Trial Outcomes & Findings for Gradual Withdrawal of Immune System Suppressing Drugs in Patients Receiving a Liver Transplant (NCT NCT00135694)

NCT ID: NCT00135694

Last Updated: 2019-02-04

Results Overview

This is a composite endpoint comprising clinical complications related to immunosuppression and is defined as the occurrence of any of the following: death or graft loss, grade 4 secondary malignancy (graded by Common Terminology Criteria for Adverse Events \[CTCAE\] version 3.0), grade 4 opportunistic infection (graded by CTCAE version 3.0), stage 3 or higher fibrosis, or decrease in renal function. Decrease in renal function is defined as: a) the estimated glomerular filtration rate (eGFR) using creatinine obtained prior to and closest to randomization will be considered the baseline and will be compared to the eGFR using creatinine obtained at 24 months +/- 3 months after randomization; b) for those with a baseline eGFR 30-90 ml per min per 1.73 meter-squared, a 25% decrease in eGFR; c) for those with a baseline eGFR greater than 90 ml per min per 1.73 meter-squared, a 25% decrease in eGFR and a decrease in eGFR to less than 90 ml per min per 1.73 meter-squared.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 275 participants
• Primary outcome timeframe: Randomization to 2 years post-randomization
• Results posted on: 2019-02-04

Participant Flow

Participants with liver failure due to hepatitis C infection or non-immune, non-viral causes were enrolled between October 2005 and April 2011.

Participants 12-24 months post-transplant, stable on immunosuppression monotherapy for at least 3 months prior to random assignment, with stage 2 or less fibrosis on the Ishak scale, adequate hepatic and renal function, and no biopsy-proven rejection were randomized between November 2006 and December 2012.

Participant milestones

Measure	Terminated Prior to Randomization Subjects enrolled and transplanted into the trial but not eligible for randomization.	Randomized to Immunosuppression Withdrawal Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal.	Randomized to Immunosuppression Maintenance Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance.
Overall Study STARTED	180	77	18
Overall Study COMPLETED	0	56	11
Overall Study NOT COMPLETED	180	21	7

Reasons for withdrawal

Measure	Terminated Prior to Randomization Subjects enrolled and transplanted into the trial but not eligible for randomization.	Randomized to Immunosuppression Withdrawal Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal.	Randomized to Immunosuppression Maintenance Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance.
Overall Study Adverse Event	17	4	0
Overall Study Death	14	1	2
Overall Study Lost to Follow-up	8	7	1
Overall Study Withdrawal by Subject	41	7	4
Overall Study Protocol Violation	19	1	0
Overall Study Hepatitis C related reasons	39	1	0
Overall Study Ineligible for Random assignment	42	0	0

Baseline Characteristics

Gradual Withdrawal of Immune System Suppressing Drugs in Patients Receiving a Liver Transplant

Baseline characteristics by cohort

Measure	Terminated Prior to Randomization n=180 Participants Subjects enrolled and transplanted into the trial but not eligible for randomization.	Randomized to Immunosuppression Withdrawal n=77 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal.	Randomized to Immunosuppression Maintenance n=18 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance.	Total n=275 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	161 Participants n=5 Participants	68 Participants n=7 Participants	13 Participants n=5 Participants	242 Participants n=4 Participants
Age, Categorical >=65 years	19 Participants n=5 Participants	9 Participants n=7 Participants	5 Participants n=5 Participants	33 Participants n=4 Participants
Age, Continuous	55.5 years STANDARD_DEVIATION 7.83 • n=5 Participants	54.3 years STANDARD_DEVIATION 9.92 • n=7 Participants	57.4 years STANDARD_DEVIATION 7.70 • n=5 Participants	55.3 years STANDARD_DEVIATION 8.47 • n=4 Participants
Sex: Female, Male Female	53 Participants n=5 Participants	14 Participants n=7 Participants	5 Participants n=5 Participants	72 Participants n=4 Participants
Sex: Female, Male Male	127 Participants n=5 Participants	63 Participants n=7 Participants	13 Participants n=5 Participants	203 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	11 Participants n=7 Participants	3 Participants n=5 Participants	24 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	167 Participants n=5 Participants	66 Participants n=7 Participants	15 Participants n=5 Participants	248 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	22 Participants n=5 Participants	7 Participants n=7 Participants	0 Participants n=5 Participants	29 Participants n=4 Participants
Race (NIH/OMB) White	153 Participants n=5 Participants	66 Participants n=7 Participants	17 Participants n=5 Participants	236 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment United States	180 participants n=5 Participants	77 participants n=7 Participants	18 participants n=5 Participants	275 participants n=4 Participants
Serum Creatinine	1.5 mg/dL STANDARD_DEVIATION 1.18 • n=5 Participants	1.3 mg/dL STANDARD_DEVIATION 0.65 • n=7 Participants	1.1 mg/dL STANDARD_DEVIATION 0.68 • n=5 Participants	1.4 mg/dL STANDARD_DEVIATION 1.04 • n=4 Participants

PRIMARY outcome

Timeframe: Randomization to 2 years post-randomization

Population: Evaluable randomized subjects having a targeted event and/or having available data for calculation of eGFR

This is a composite endpoint comprising clinical complications related to immunosuppression and is defined as the occurrence of any of the following: death or graft loss, grade 4 secondary malignancy (graded by Common Terminology Criteria for Adverse Events [CTCAE] version 3.0), grade 4 opportunistic infection (graded by CTCAE version 3.0), stage 3 or higher fibrosis, or decrease in renal function. Decrease in renal function is defined as: a) the estimated glomerular filtration rate (eGFR) using creatinine obtained prior to and closest to randomization will be considered the baseline and will be compared to the eGFR using creatinine obtained at 24 months +/- 3 months after randomization; b) for those with a baseline eGFR 30-90 ml per min per 1.73 meter-squared, a 25% decrease in eGFR; c) for those with a baseline eGFR greater than 90 ml per min per 1.73 meter-squared, a 25% decrease in eGFR and a decrease in eGFR to less than 90 ml per min per 1.73 meter-squared.

Outcome measures

Measure	Randomized to Immunosuppression Withdrawal n=66 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal.	Randomized to Immunosuppression Maintenance n=13 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance.
Number of Participants With Clinical Complications Usually Attributed to Immunosuppression	12 participants	4 participants

SECONDARY outcome

Timeframe: One to two years post-transplantation

Population: All subjects transplanted

Outcome measures

Measure	Randomized to Immunosuppression Withdrawal n=275 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal.	Randomized to Immunosuppression Maintenance Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance.
Number of Participants Who Qualify for Random Assignment	95 participants	—

SECONDARY outcome

Timeframe: Randomization until study completion or participant termination (up to six years post-transplant)

Population: Participants randomized to immunosuppression withdrawal

Outcome measures

Measure	Randomized to Immunosuppression Withdrawal n=77 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal.	Randomized to Immunosuppression Maintenance Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance.
Number of Participants Who Successfully Stop Taking Immunosuppression for at Least 6 Months	12 participants	—

SECONDARY outcome

Timeframe: Discontinuation of all immunosuppression to end of trial participation or to time of restarting immunosuppression, whichever came first, assessed up to two years

Population: Participants randomized to immunosuppression withdrawal who completed withdrawal and discontinued all immunosuppression

Time (in days) from withdrawing off of all immunosuppressive drugs to re-starting immunosuppression or study termination/completion.

Outcome measures

Measure	Randomized to Immunosuppression Withdrawal n=14 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal.	Randomized to Immunosuppression Maintenance Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance.
Immunosuppression-free Duration	555.2 Days Interval 36.0 to 790.0	—

SECONDARY outcome

Timeframe: Randomization to 2 years post-randomization.

Population: Hepatitis C infected participants randomized.

Number of subjects with a biopsy showing stage 4 fibrosis or higher on the Ishak scale. Stage 4 represents at least 13.7% fibrosis measurement with a description of fibrous expansion of portal areas with marked bridging (P-P) as well as portal to central (P-C). Stage 5 is marked bridging (P-P and/or P-C), with occasional nodules (incomplete cirrhosis) and stage 6 is cirrhosis, probable or definite.

Outcome measures

Measure	Randomized to Immunosuppression Withdrawal n=30 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal.	Randomized to Immunosuppression Maintenance n=7 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance.
Number of Hepatitis C Infected Participants With Progression of Hepatitis C Related Liver Disease, Defined as Stage 4 or Higher Fibrosis on the Ishak Scale	0 participants	0 participants

SECONDARY outcome

Timeframe: Randomization to 2 years post-randomization.

Population: Randomized participants (intent-to-treat sample)

Number of participants with graft loss or death. Graft loss is defined as subject death or re-transplantation.

Outcome measures

Measure	Randomized to Immunosuppression Withdrawal n=77 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal.	Randomized to Immunosuppression Maintenance n=18 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance.
Number of Participants Experiencing Graft Loss or Death	1 participants	0 participants

SECONDARY outcome

Timeframe: Month 21 to Month 24 post-randomization

Population: Randomized participants still being followed 24 months post-randomization.

Daily immunosuppression score in units per day averaged over the 3-month period from Month 21 to Month 24 post-randomization. Daily doses were assigned a score of 1 unit as follows: tacrolimus 1 mg, cyclosporine 100 mg, Sirolimus 1 mg, mycophenolate mofetil 1000 mg, Mycophenolic acid 720 mg, azathioprine 50 mg, and prednisone 5 mg. Any antibody use equaled 20 units. Unit scores based on Vasudev (Vasudev B, Hariharan S, Hussain SA, Zhu YR, Bresnahan BA et al. BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients. Kidney Int. 2005; 8(4):1834-1839.)

Outcome measures

Measure	Randomized to Immunosuppression Withdrawal n=64 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal.	Randomized to Immunosuppression Maintenance n=13 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance.
Total Immunosuppression From Month 21 to Month 24 Post-randomization	2.8 units per day Interval 0.0 to 10.0	3.7 units per day Interval 1.5 to 8.0

SECONDARY outcome

Timeframe: Randomization to Month 24 post-randomization

Population: Randomized participants still being followed 24 months post-randomization.

Total immunosuppression score in units taken as the sum of units per day over the 2-year period from randomization to Month 24 post-randomization. Daily doses were assigned a score of 1 unit as follows: tacrolimus 1 mg, cyclosporine 100 mg, Sirolimus 1 mg, mycophenolate mofetil 1000 mg, Mycophenolic acid 720 mg, azathioprine 50 mg, and prednisone 5 mg. Any antibody use equaled 20 units. Unit scores based on Vasudev (Vasudev B, Hariharan S, Hussain SA, Zhu YR, Bresnahan BA et al. BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients. Kidney Int. 2005; 8(4):1834-1839.).

Outcome measures

Measure	Randomized to Immunosuppression Withdrawal n=64 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal.	Randomized to Immunosuppression Maintenance n=13 Participants Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance.
Total Burden of Immunosuppression From Random Assignment to Month 24	2198.5 units Interval 255.0 to 4604.0	2708.4 units Interval 1126.0 to 6853.0

Adverse Events

Terminated Prior to Randomization

Serious events: 89 serious events

Other events: 155 other events

Deaths: 0 deaths

Randomized to Immunosuppression Withdrawal

Serious events: 9 serious events

Other events: 18 other events

Deaths: 0 deaths

Randomized to Immunosuppression Maintenance

Serious events: 54 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Measure	Terminated Prior to Randomization n=180 participants at risk Subjects enrolled and transplanted into the trial but not eligible for randomization.	Randomized to Immunosuppression Withdrawal n=18 participants at risk Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal.	Randomized to Immunosuppression Maintenance n=77 participants at risk Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance.
Blood and lymphatic system disorders Anaemia	3.9% 7/180 • Number of events 7 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Blood and lymphatic system disorders Coagulopathy	0.56% 1/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Blood and lymphatic system disorders Leukocytosis	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Blood and lymphatic system disorders Neutropenia	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Blood and lymphatic system disorders Pancytopenia	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Blood and lymphatic system disorders Thrombocytopenia	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Cardiac disorders Angina pectoris	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Cardiac disorders Angina unstable	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Cardiac disorders Atrial fibrillation	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	11.1% 2/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Cardiac disorders Atrioventricular block complete	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Cardiac disorders Cardiac arrest	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Cardiac disorders Cardiac failure	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Cardiac disorders Cardiac failure acute	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Cardiac disorders Cardiac failure congestive	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Cardiac disorders Cardio-respiratory arrest	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Cardiac disorders Coronary artery disease	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Cardiac disorders Myocardial infarction	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Cardiac disorders Pericardial effusion	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Cardiac disorders Supraventricular extrasystoles	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Cardiac disorders Supraventricular tachycardia	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Cardiac disorders Ventricular tachycardia	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Endocrine disorders Hypothyroidism	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Abdominal distension	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Abdominal hernia	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Abdominal pain	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 3 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Ascites	2.2% 4/180 • Number of events 6 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Diarrhoea	1.1% 2/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Femoral hernia, obstructive	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Food poisoning	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Ileus	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Inguinal hernia	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Inguinal hernia, obstructive	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Intestinal strangulation	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Intra-abdominal haemorrhage	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Large intestine perforation	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Nausea	1.7% 3/180 • Number of events 5 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Oesophageal varices haemorrhage	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Pancreatitis necrotising	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Peritoneal effusion	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Rectal haemorrhage	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Retroperitoneal haemorrhage	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Small intestinal obstruction	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Umbilical hernia	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Vomiting	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
General disorders Chest pain	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
General disorders Death	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
General disorders Fatigue	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
General disorders Hernia obstructive	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
General disorders Oedema peripheral	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
General disorders Pyrexia	2.8% 5/180 • Number of events 6 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Hepatobiliary disorders Bile duct obstruction	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Hepatobiliary disorders Bile duct stenosis	0.00% 0/180 • Enrollment through end of study (up to 7 years)	11.1% 2/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Hepatobiliary disorders Cholangitis	2.2% 4/180 • Number of events 5 • Enrollment through end of study (up to 7 years)	11.1% 2/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Hepatobiliary disorders Cholelithiasis	0.56% 1/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Hepatobiliary disorders Cholestasis	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Hepatobiliary disorders Chronic hepatic failure	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Hepatobiliary disorders Hepatic artery stenosis	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Hepatobiliary disorders Hepatic cirrhosis	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Hepatobiliary disorders Hepatic steatosis	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Hepatobiliary disorders Hepatitis cholestatic	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Hepatobiliary disorders Hepatorenal syndrome	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Immune system disorders Graft versus host disease	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Immune system disorders Transplant rejection	14.4% 26/180 • Number of events 28 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	27.3% 21/77 • Number of events 25 • Enrollment through end of study (up to 7 years)
Infections and infestations Abdominal abscess	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Infections and infestations Aspergillosis	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Bacteraemia	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Infections and infestations Beta haemolytic streptococcal infection	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Infections and infestations Brain abscess	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Bronchopulmonary aspergillosis	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Catheter related infection	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Cellulitis	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Infections and infestations Clostridial infection	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Infections and infestations Clostridium difficile colitis	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Coxsackie viral infection	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Infections and infestations Cryptococcosis	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Cytomegalovirus colitis	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Cytomegalovirus infection	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Infections and infestations Diverticulitis	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Empyema	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Infections and infestations Enterococcal bacteraemia	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Escherichia bacteraemia	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Gastroenteritis	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Groin abscess	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Infections and infestations Hepatitis C	3.9% 7/180 • Number of events 7 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Herpes simplex	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Infections and infestations Liver abscess	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Meningitis cryptococcal	0.56% 1/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Perihepatic abscess	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Infections and infestations Peritonitis bacterial	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Infections and infestations Pneumonia	0.56% 1/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Infections and infestations Pneumonia staphylococcal	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Postoperative wound infection	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Sepsis	4.4% 8/180 • Number of events 8 • Enrollment through end of study (up to 7 years)	11.1% 2/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Infections and infestations Streptococcal bacteraemia	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Infections and infestations Urinary tract infection	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	3.9% 3/77 • Number of events 3 • Enrollment through end of study (up to 7 years)
Infections and infestations Viral diarrhoea	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Viral infection	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Infections and infestations Wound infection	2.2% 4/180 • Number of events 4 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Biliary anastomosis complication	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Fall	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Graft dysfunction	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Hip fracture	0.56% 1/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Incisional hernia	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	7.8% 6/77 • Number of events 6 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Injury	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Medical device complication	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Poisoning	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Post procedural bile leak	3.9% 7/180 • Number of events 7 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Post procedural haemorrhage	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Procedural complication	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Therapeutic agent toxicity	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Vascular pseudoaneurysm	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Wound dehiscence	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Wound secretion	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Investigations Alanine aminotransferase increased	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Investigations Aspartate aminotransferase increased	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Investigations Blood alkaline phosphatase increased	0.56% 1/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Investigations Blood bilirubin increased	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Investigations Blood creatinine increased	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Investigations Electrocardiogram T wave inversion	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Investigations Gamma-glutamyltransferase increased	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Investigations Hepatic enzyme increased	2.2% 4/180 • Number of events 4 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Investigations Liver function test abnormal	2.2% 4/180 • Number of events 4 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Investigations Transaminases increased	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Dehydration	2.8% 5/180 • Number of events 6 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	6.5% 5/77 • Number of events 5 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Diabetes mellitus	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Fluid overload	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Hyperglycaemia	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Hyperkalaemia	5.0% 9/180 • Number of events 11 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Hypoglycaemic seizure	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Hyponatraemia	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Obesity	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Musculoskeletal and connective tissue disorders Muscular weakness	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Musculoskeletal and connective tissue disorders Polyarthritis	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant recurrent	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Multiple myeloma	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Nervous system disorders Central pontine myelinolysis	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Nervous system disorders Cerebral haemorrhage	1.7% 3/180 • Number of events 4 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Nervous system disorders Cerebral infarction	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Nervous system disorders Cerebrovascular accident	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Nervous system disorders Convulsion	2.8% 5/180 • Number of events 5 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Nervous system disorders Haemorrhagic stroke	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Nervous system disorders Hepatic encephalopathy	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Nervous system disorders Lacunar infarction	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Nervous system disorders Reversible posterior leukoencephalopathy syndrome	0.56% 1/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Psychiatric disorders Confusional state	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Psychiatric disorders Mental disorder due to a general medical condition	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Psychiatric disorders Mental status changes	2.2% 4/180 • Number of events 4 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Psychiatric disorders Suicide attempt	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Renal and urinary disorders Anuria	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Renal and urinary disorders Calculus ureteric	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Renal and urinary disorders Haematuria	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Renal and urinary disorders Renal failure	2.2% 4/180 • Number of events 4 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Renal and urinary disorders Renal failure acute	2.8% 5/180 • Number of events 5 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	3.9% 3/77 • Number of events 5 • Enrollment through end of study (up to 7 years)
Renal and urinary disorders Renal failure chronic	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Renal and urinary disorders Tubulointerstitial nephritis	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.2% 4/180 • Number of events 4 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	3.9% 3/77 • Number of events 3 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Haemothorax	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.2% 4/180 • Number of events 5 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Pulmonary cavitation	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.2% 4/180 • Number of events 4 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Skin and subcutaneous tissue disorders Rash	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Social circumstances Treatment noncompliance	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Surgical and medical procedures Gastrectomy	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Surgical and medical procedures Haematoma evacuation	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Surgical and medical procedures Inguinal hernia repair	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Surgical and medical procedures Medical device change	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Surgical and medical procedures Small intestinal resection	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Surgical and medical procedures Spinal fusion surgery	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Vascular disorders Deep vein thrombosis	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Vascular disorders Haemorrhage	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Vascular disorders Hypertension	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Vascular disorders Hypotension	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Vascular disorders Venous thrombosis	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)

Other adverse events

Measure	Terminated Prior to Randomization n=180 participants at risk Subjects enrolled and transplanted into the trial but not eligible for randomization.	Randomized to Immunosuppression Withdrawal n=18 participants at risk Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal.	Randomized to Immunosuppression Maintenance n=77 participants at risk Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance.
Blood and lymphatic system disorders Anaemia	15.0% 27/180 • Number of events 37 • Enrollment through end of study (up to 7 years)	16.7% 3/18 • Number of events 3 • Enrollment through end of study (up to 7 years)	14.3% 11/77 • Number of events 14 • Enrollment through end of study (up to 7 years)
Blood and lymphatic system disorders Neutropenia	3.9% 7/180 • Number of events 7 • Enrollment through end of study (up to 7 years)	11.1% 2/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Cardiac disorders Bradycardia	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Ear and labyrinth disorders Ear pain	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Eye disorders Ocular icterus	3.3% 6/180 • Number of events 6 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Eye disorders Visual impairment	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Abdominal distension	3.9% 7/180 • Number of events 7 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	3.9% 3/77 • Number of events 3 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Abdominal hernia	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	16.7% 3/18 • Number of events 3 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Abdominal pain	5.0% 9/180 • Number of events 11 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	9.1% 7/77 • Number of events 7 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Abdominal pain upper	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Ascites	7.2% 13/180 • Number of events 15 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Constipation	3.3% 6/180 • Number of events 7 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	7.8% 6/77 • Number of events 8 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Diarrhoea	13.9% 25/180 • Number of events 28 • Enrollment through end of study (up to 7 years)	11.1% 2/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	16.9% 13/77 • Number of events 18 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Dyspepsia	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 5 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Nausea	6.1% 11/180 • Number of events 12 • Enrollment through end of study (up to 7 years)	11.1% 2/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	13.0% 10/77 • Number of events 13 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Umbilical hernia	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Gastrointestinal disorders Vomiting	3.3% 6/180 • Number of events 6 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	11.7% 9/77 • Number of events 11 • Enrollment through end of study (up to 7 years)
General disorders Asthenia	2.2% 4/180 • Number of events 4 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
General disorders Fatigue	4.4% 8/180 • Number of events 9 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	10.4% 8/77 • Number of events 9 • Enrollment through end of study (up to 7 years)
General disorders Influenza like illness	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	6.5% 5/77 • Number of events 7 • Enrollment through end of study (up to 7 years)
General disorders Oedema	6.7% 12/180 • Number of events 14 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	6.5% 5/77 • Number of events 5 • Enrollment through end of study (up to 7 years)
General disorders Oedema peripheral	23.9% 43/180 • Number of events 45 • Enrollment through end of study (up to 7 years)	22.2% 4/18 • Number of events 4 • Enrollment through end of study (up to 7 years)	20.8% 16/77 • Number of events 18 • Enrollment through end of study (up to 7 years)
General disorders Pyrexia	8.3% 15/180 • Number of events 17 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	16.9% 13/77 • Number of events 17 • Enrollment through end of study (up to 7 years)
Hepatobiliary disorders Bile duct stenosis	4.4% 8/180 • Number of events 8 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	7.8% 6/77 • Number of events 6 • Enrollment through end of study (up to 7 years)
Hepatobiliary disorders Biloma	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Hepatobiliary disorders Cholestasis	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Immune system disorders Hypersensitivity	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Immune system disorders Transplant rejection	10.0% 18/180 • Number of events 18 • Enrollment through end of study (up to 7 years)	11.1% 2/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	19.5% 15/77 • Number of events 15 • Enrollment through end of study (up to 7 years)
Infections and infestations Bronchitis	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	6.5% 5/77 • Number of events 5 • Enrollment through end of study (up to 7 years)
Infections and infestations Cellulitis	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	9.1% 7/77 • Number of events 7 • Enrollment through end of study (up to 7 years)
Infections and infestations Escherichia bacteraemia	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Infections and infestations Gastroenteritis viral	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 6 • Enrollment through end of study (up to 7 years)
Infections and infestations Hepatitis C	19.4% 35/180 • Number of events 35 • Enrollment through end of study (up to 7 years)	11.1% 2/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	20.8% 16/77 • Number of events 16 • Enrollment through end of study (up to 7 years)
Infections and infestations Herpes zoster	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Infections and infestations Nasopharyngitis	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 5 • Enrollment through end of study (up to 7 years)
Infections and infestations Pneumonia	3.3% 6/180 • Number of events 6 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	6.5% 5/77 • Number of events 5 • Enrollment through end of study (up to 7 years)
Infections and infestations Sinusitis	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	9.1% 7/77 • Number of events 8 • Enrollment through end of study (up to 7 years)
Infections and infestations Upper respiratory tract infection	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	10.4% 8/77 • Number of events 11 • Enrollment through end of study (up to 7 years)
Infections and infestations Urinary tract infection	7.8% 14/180 • Number of events 16 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	13.0% 10/77 • Number of events 22 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Biliary anastomosis complication	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Concussion	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Foot fracture	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Incision site complication	4.4% 8/180 • Number of events 8 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	7.8% 6/77 • Number of events 6 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Incision site pain	2.8% 5/180 • Number of events 5 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	7.8% 6/77 • Number of events 7 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Incisional hernia	3.3% 6/180 • Number of events 6 • Enrollment through end of study (up to 7 years)	16.7% 3/18 • Number of events 3 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Post procedural bile leak	7.8% 14/180 • Number of events 15 • Enrollment through end of study (up to 7 years)	11.1% 2/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Rib fracture	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Investigations Alanine aminotransferase increased	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	7.8% 6/77 • Number of events 10 • Enrollment through end of study (up to 7 years)
Investigations Aspartate aminotransferase increased	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	6.5% 5/77 • Number of events 9 • Enrollment through end of study (up to 7 years)
Investigations Blood alkaline phosphatase increased	1.7% 3/180 • Number of events 4 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	7.8% 6/77 • Number of events 7 • Enrollment through end of study (up to 7 years)
Investigations Blood bilirubin increased	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	3.9% 3/77 • Number of events 5 • Enrollment through end of study (up to 7 years)
Investigations Blood creatinine increased	4.4% 8/180 • Number of events 8 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	10.4% 8/77 • Number of events 8 • Enrollment through end of study (up to 7 years)
Investigations Blood glucose increased	2.2% 4/180 • Number of events 4 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Investigations Breath sounds abnormal	6.1% 11/180 • Number of events 12 • Enrollment through end of study (up to 7 years)	16.7% 3/18 • Number of events 3 • Enrollment through end of study (up to 7 years)	14.3% 11/77 • Number of events 12 • Enrollment through end of study (up to 7 years)
Investigations Eosinophil count increased	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Investigations Gamma-glutamyltransferase increased	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	6.5% 5/77 • Number of events 7 • Enrollment through end of study (up to 7 years)
Investigations Haematocrit decreased	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Investigations Haemoglobin decreased	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Investigations Hepatic enzyme increased	3.9% 7/180 • Number of events 7 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	11.7% 9/77 • Number of events 9 • Enrollment through end of study (up to 7 years)
Investigations International normalised ratio increased	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	3.9% 3/77 • Number of events 3 • Enrollment through end of study (up to 7 years)
Investigations Liver function test abnormal	7.8% 14/180 • Number of events 14 • Enrollment through end of study (up to 7 years)	16.7% 3/18 • Number of events 4 • Enrollment through end of study (up to 7 years)	32.5% 25/77 • Number of events 32 • Enrollment through end of study (up to 7 years)
Investigations Lymphocyte count decreased	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Investigations Red blood cell count decreased	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Investigations Weight increased	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	6.5% 5/77 • Number of events 5 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Dehydration	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Diabetes mellitus	16.1% 29/180 • Number of events 29 • Enrollment through end of study (up to 7 years)	11.1% 2/18 • Number of events 3 • Enrollment through end of study (up to 7 years)	26.0% 20/77 • Number of events 20 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Gout	0.56% 1/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	3.9% 3/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Hyperglycaemia	10.6% 19/180 • Number of events 19 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	19.5% 15/77 • Number of events 17 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Hyperkalaemia	15.6% 28/180 • Number of events 35 • Enrollment through end of study (up to 7 years)	16.7% 3/18 • Number of events 3 • Enrollment through end of study (up to 7 years)	29.9% 23/77 • Number of events 28 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Hyperphosphataemia	1.1% 2/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Hypomagnesaemia	7.8% 14/180 • Number of events 14 • Enrollment through end of study (up to 7 years)	11.1% 2/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	16.9% 13/77 • Number of events 14 • Enrollment through end of study (up to 7 years)
Metabolism and nutrition disorders Metabolic syndrome	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Musculoskeletal and connective tissue disorders Arthralgia	2.8% 5/180 • Number of events 5 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	9.1% 7/77 • Number of events 7 • Enrollment through end of study (up to 7 years)
Musculoskeletal and connective tissue disorders Back pain	2.2% 4/180 • Number of events 4 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	13.0% 10/77 • Number of events 10 • Enrollment through end of study (up to 7 years)
Musculoskeletal and connective tissue disorders Muscle spasms	2.8% 5/180 • Number of events 5 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 5 • Enrollment through end of study (up to 7 years)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.7% 3/180 • Number of events 4 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Musculoskeletal and connective tissue disorders Neck pain	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	9.1% 7/77 • Number of events 7 • Enrollment through end of study (up to 7 years)
Musculoskeletal and connective tissue disorders Pain in extremity	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/180 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Nervous system disorders Convulsion	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Nervous system disorders Dizziness	2.2% 4/180 • Number of events 5 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Nervous system disorders Encephalopathy	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Nervous system disorders Headache	7.2% 13/180 • Number of events 13 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	14.3% 11/77 • Number of events 15 • Enrollment through end of study (up to 7 years)
Nervous system disorders Hypoaesthesia	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Nervous system disorders Neuropathy peripheral	1.7% 3/180 • Number of events 3 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	6.5% 5/77 • Number of events 5 • Enrollment through end of study (up to 7 years)
Nervous system disorders Tremor	6.1% 11/180 • Number of events 12 • Enrollment through end of study (up to 7 years)	11.1% 2/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	11.7% 9/77 • Number of events 13 • Enrollment through end of study (up to 7 years)
Psychiatric disorders Confusional state	5.6% 10/180 • Number of events 10 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Psychiatric disorders Depression	3.3% 6/180 • Number of events 6 • Enrollment through end of study (up to 7 years)	16.7% 3/18 • Number of events 5 • Enrollment through end of study (up to 7 years)	6.5% 5/77 • Number of events 5 • Enrollment through end of study (up to 7 years)
Psychiatric disorders Insomnia	3.3% 6/180 • Number of events 6 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	7.8% 6/77 • Number of events 7 • Enrollment through end of study (up to 7 years)
Renal and urinary disorders Renal failure	15.0% 27/180 • Number of events 27 • Enrollment through end of study (up to 7 years)	16.7% 3/18 • Number of events 3 • Enrollment through end of study (up to 7 years)	19.5% 15/77 • Number of events 16 • Enrollment through end of study (up to 7 years)
Renal and urinary disorders Renal failure acute	6.7% 12/180 • Number of events 13 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Renal and urinary disorders Renal tubular necrosis	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Cough	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.3% 6/180 • Number of events 7 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	7.8% 6/77 • Number of events 6 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Pleural effusion	8.3% 15/180 • Number of events 16 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	7.8% 6/77 • Number of events 6 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.1% 2/180 • Number of events 2 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Productive cough	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/18 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 4 • Enrollment through end of study (up to 7 years)
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Skin and subcutaneous tissue disorders Cold sweat	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Skin and subcutaneous tissue disorders Erythema	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Skin and subcutaneous tissue disorders Precancerous skin lesion	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Skin and subcutaneous tissue disorders Pruritus	3.9% 7/180 • Number of events 8 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	6.5% 5/77 • Number of events 6 • Enrollment through end of study (up to 7 years)
Skin and subcutaneous tissue disorders Rash	2.8% 5/180 • Number of events 5 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	5.2% 4/77 • Number of events 5 • Enrollment through end of study (up to 7 years)
Skin and subcutaneous tissue disorders Skin ulcer	0.56% 1/180 • Number of events 1 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	1.3% 1/77 • Number of events 1 • Enrollment through end of study (up to 7 years)
Surgical and medical procedures Finger amputation	0.00% 0/180 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	0.00% 0/77 • Enrollment through end of study (up to 7 years)
Vascular disorders Hypertension	6.7% 12/180 • Number of events 12 • Enrollment through end of study (up to 7 years)	11.1% 2/18 • Number of events 2 • Enrollment through end of study (up to 7 years)	11.7% 9/77 • Number of events 9 • Enrollment through end of study (up to 7 years)
Vascular disorders Hypotension	2.8% 5/180 • Number of events 5 • Enrollment through end of study (up to 7 years)	5.6% 1/18 • Number of events 1 • Enrollment through end of study (up to 7 years)	2.6% 2/77 • Number of events 2 • Enrollment through end of study (up to 7 years)

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: DAITClinicalTrialsGov@niaid.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place