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Trial Outcomes & Findings for Study Evaluating of Calcineurin Inhibitor and Sirolimus (Rapamune) Treatment in Liver Transplant Recipients (NCT NCT00086346)

NCT ID: NCT00086346

Last Updated: 2010-04-28

Results Overview

GFR is an index of kidney function. GFR was calculated using Cockcroft-Gault method. A normal GFR is \>90 mL/min, higher values indicate better function. Change=adjusted mean of 12 months minus baseline. Mean adjusted for baseline GFR, with antimetabolite therapy status and hepatitis C status as fixed effects.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

607 participants

Primary outcome timeframe

Baseline and 12 months

Results posted on

2010-04-28

Participant Flow

Patients were recruited October 2002 to November 2006.

Patients were screened up to 30 days.

Participant milestones

Participant milestones
Measure
Sirolimus (SRL) Conversion
Sirolimus was administered once daily. A loading dose of sirolimus, 10 to 15 mg, was administered in divided doses on day 1: the first dose was given after collection of the sirolimus trough level and a minimum of 4 hours following the last dose of CNI, and the second dose approximately 12 hours after the first dose. On days 2 through 6, sirolimus was administered in a dose of 3 to 5 mg/day. For the remaining study period, day 7 through month 72, appropriate daily doses of sirolimus were administered to attain the recommended trough concentrations of 8 to 16 ng/mL (using a chromatographic method) or 10 to 20 ng/mL (using an immunoassay).
Calcineurin Inhibitors (CNI) Continuation
Calcineurin Inhibitors administered per local practice to attain target trough levels of 3 to 10 ng/mL (tacrolimus) or 50 to 250 ng/mL (cyclosporin A), respectively.
Randomization
STARTED
393
214
Randomization
COMPLETED
389
210
Randomization
NOT COMPLETED
4
4
Patients Dosed With Test Article
STARTED
389
210
Patients Dosed With Test Article
COMPLETED
249
187
Patients Dosed With Test Article
NOT COMPLETED
140
23

Reasons for withdrawal

Reasons for withdrawal
Measure
Sirolimus (SRL) Conversion
Sirolimus was administered once daily. A loading dose of sirolimus, 10 to 15 mg, was administered in divided doses on day 1: the first dose was given after collection of the sirolimus trough level and a minimum of 4 hours following the last dose of CNI, and the second dose approximately 12 hours after the first dose. On days 2 through 6, sirolimus was administered in a dose of 3 to 5 mg/day. For the remaining study period, day 7 through month 72, appropriate daily doses of sirolimus were administered to attain the recommended trough concentrations of 8 to 16 ng/mL (using a chromatographic method) or 10 to 20 ng/mL (using an immunoassay).
Calcineurin Inhibitors (CNI) Continuation
Calcineurin Inhibitors administered per local practice to attain target trough levels of 3 to 10 ng/mL (tacrolimus) or 50 to 250 ng/mL (cyclosporin A), respectively.
Randomization
Did not receive test article
4
4
Patients Dosed With Test Article
Adverse Event
94
11
Patients Dosed With Test Article
Lost to Follow-up
1
3
Patients Dosed With Test Article
Nonmedical event
7
3
Patients Dosed With Test Article
Withdrawal by Subject
16
3
Patients Dosed With Test Article
Protocol Violation
11
3
Patients Dosed With Test Article
Lack of Efficacy
11
0

Baseline Characteristics

Study Evaluating of Calcineurin Inhibitor and Sirolimus (Rapamune) Treatment in Liver Transplant Recipients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Sirolimus (SRL) Conversion
n=393 Participants
Sirolimus was administered once daily. A loading dose of sirolimus, 10 to 15 mg, was administered in divided doses on day 1: the first dose was given after collection of the sirolimus trough level and a minimum of 4 hours following the last dose of CNI, and the second dose approximately 12 hours after the first dose. On days 2 through 6, sirolimus was administered in a dose of 3 to 5 mg/day. For the remaining study period, day 7 through month 72, appropriate daily doses of sirolimus were administered to attain the recommended trough concentrations of 8 to 16 ng/mL (using a chromatographic method) or 10 to 20 ng/mL (using an immunoassay).
Calcineurin Inhibitors (CNI) Continuation
n=214 Participants
Calcineurin Inhibitors administered per local practice to attain target trough levels of 3 to 10 ng/mL (tacrolimus) or 50 to 250 ng/mL (cyclosporin A), respectively.
Total
n=607 Participants
Total of all reporting groups
Age Continuous
57.0 years
n=5 Participants
56.5 years
n=7 Participants
57.0 years
n=5 Participants
Sex: Female, Male
Female
122 Participants
n=5 Participants
64 Participants
n=7 Participants
186.0 Participants
n=5 Participants
Sex: Female, Male
Male
271 Participants
n=5 Participants
150 Participants
n=7 Participants
421.0 Participants
n=5 Participants
Mean serum creatinine levels
122.9 μmol/L
STANDARD_DEVIATION 32.3 • n=5 Participants
125.2 μmol/L
STANDARD_DEVIATION 31.9 • n=7 Participants
123.7 μmol/L
STANDARD_DEVIATION 32.2 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 12 months

Population: The intent to treat population was analyzed and consisted of all patients randomly assigned to treatment. Patients were stratified by hepatitis C status and whether or not they were receiving antimetabolite therapy at time of randomization.

GFR is an index of kidney function. GFR was calculated using Cockcroft-Gault method. A normal GFR is \>90 mL/min, higher values indicate better function. Change=adjusted mean of 12 months minus baseline. Mean adjusted for baseline GFR, with antimetabolite therapy status and hepatitis C status as fixed effects.

Outcome measures

Outcome measures
Measure
Sirolimus (SRL) Conversion
n=393 Participants
Sirolimus was administered once daily. A loading dose of sirolimus, 10 to 15 mg, was administered in divided doses on day 1: the first dose was given after collection of the sirolimus trough level and a minimum of 4 hours following the last dose of CNI, and the second dose approximately 12 hours after the first dose. On days 2 through 6, sirolimus was administered in a dose of 3 to 5 mg/day. For the remaining study period, day 7 through month 72, appropriate daily doses of sirolimus were administered to attain the recommended trough concentrations of 8 to 16 ng/mL (using a chromatographic method) or 10 to 20 ng/mL (using an immunoassay).
Calcineurin Inhibitors (CNI) Continuation
n=214 Participants
Calcineurin Inhibitors administered per local practice to attain target trough levels of 3 to 10 ng/mL (tacrolimus) or 50 to 250 ng/mL (cyclosporin A), respectively.
Change From Baseline Adjusted Mean in Glomerular Filtration Rate (GFR)
-4.45 mL/min
Standard Error 1.12
-3.07 mL/min
Standard Error 1.36

PRIMARY outcome

Timeframe: 12 months

Population: Intent to treat analysis population with stratification by antimetabolite therapy and hepatitis C status.

Endpoint was a composite assessment of patient and graft survival. Patients categorized as graft survival or graft loss. Graft loss defined as pure graft loss (requiring retransplant) or death (with a functioning graft), if the event occurred in the first 12 months after randomization. Patients with missing graft data were counted as graft losses.

Outcome measures

Outcome measures
Measure
Sirolimus (SRL) Conversion
n=393 Participants
Sirolimus was administered once daily. A loading dose of sirolimus, 10 to 15 mg, was administered in divided doses on day 1: the first dose was given after collection of the sirolimus trough level and a minimum of 4 hours following the last dose of CNI, and the second dose approximately 12 hours after the first dose. On days 2 through 6, sirolimus was administered in a dose of 3 to 5 mg/day. For the remaining study period, day 7 through month 72, appropriate daily doses of sirolimus were administered to attain the recommended trough concentrations of 8 to 16 ng/mL (using a chromatographic method) or 10 to 20 ng/mL (using an immunoassay).
Calcineurin Inhibitors (CNI) Continuation
n=214 Participants
Calcineurin Inhibitors administered per local practice to attain target trough levels of 3 to 10 ng/mL (tacrolimus) or 50 to 250 ng/mL (cyclosporin A), respectively.
Patient and Graft Survival
Graft loss: Pure (with retransplant)
0 patients
0 patients
Patient and Graft Survival
Graft survival
367 patients
202 patients
Patient and Graft Survival
Graft loss (total)
26 patients
12 patients
Patient and Graft Survival
Graft loss: Death
13 patients
3 patients
Patient and Graft Survival
Graft loss: Incomplete data
13 patients
9 patients

SECONDARY outcome

Timeframe: 12 months

Population: The analysis population is the intent to treat. Any patient whose clinical rejection data was incomplete was designated as an acute rejection in the analysis.

Overall event rate is determined as yes or no.

Outcome measures

Outcome measures
Measure
Sirolimus (SRL) Conversion
n=393 Participants
Sirolimus was administered once daily. A loading dose of sirolimus, 10 to 15 mg, was administered in divided doses on day 1: the first dose was given after collection of the sirolimus trough level and a minimum of 4 hours following the last dose of CNI, and the second dose approximately 12 hours after the first dose. On days 2 through 6, sirolimus was administered in a dose of 3 to 5 mg/day. For the remaining study period, day 7 through month 72, appropriate daily doses of sirolimus were administered to attain the recommended trough concentrations of 8 to 16 ng/mL (using a chromatographic method) or 10 to 20 ng/mL (using an immunoassay).
Calcineurin Inhibitors (CNI) Continuation
n=214 Participants
Calcineurin Inhibitors administered per local practice to attain target trough levels of 3 to 10 ng/mL (tacrolimus) or 50 to 250 ng/mL (cyclosporin A), respectively.
Number of Patients With a Biopsy Confirmed Acute Rejection
Yes
46 patients
13 patients
Number of Patients With a Biopsy Confirmed Acute Rejection
No
347 patients
201 patients

SECONDARY outcome

Timeframe: 12 months

Population: On-therapy population; consisted of patients who were still receiving study medication at the defined endpoint.

Observed mean values for serum creatinine.

Outcome measures

Outcome measures
Measure
Sirolimus (SRL) Conversion
n=262 Participants
Sirolimus was administered once daily. A loading dose of sirolimus, 10 to 15 mg, was administered in divided doses on day 1: the first dose was given after collection of the sirolimus trough level and a minimum of 4 hours following the last dose of CNI, and the second dose approximately 12 hours after the first dose. On days 2 through 6, sirolimus was administered in a dose of 3 to 5 mg/day. For the remaining study period, day 7 through month 72, appropriate daily doses of sirolimus were administered to attain the recommended trough concentrations of 8 to 16 ng/mL (using a chromatographic method) or 10 to 20 ng/mL (using an immunoassay).
Calcineurin Inhibitors (CNI) Continuation
n=190 Participants
Calcineurin Inhibitors administered per local practice to attain target trough levels of 3 to 10 ng/mL (tacrolimus) or 50 to 250 ng/mL (cyclosporin A), respectively.
Mean Serum Creatinine
119.0 µmol/L
Standard Deviation 38.9
122.4 µmol/L
Standard Deviation 31.5

Adverse Events

Sirolimus (SRL) Conversion

Serious events: 193 serious events
Other events: 386 other events
Deaths: 0 deaths

Calcineurin Inhibitors (CNI) Continuation

Serious events: 79 serious events
Other events: 201 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Sirolimus (SRL) Conversion
n=389 participants at risk
Sirolimus was administered once daily. A loading dose of sirolimus, 10 to 15 mg, was administered in divided doses on day 1: the first dose was given after collection of the sirolimus trough level and a minimum of 4 hours following the last dose of CNI, and the second dose approximately 12 hours after the first dose. On days 2 through 6, sirolimus was administered in a dose of 3 to 5 mg/day. For the remaining study period, day 7 through month 72, appropriate daily doses of sirolimus were administered to attain the recommended trough concentrations of 8 to 16 ng/mL (using a chromatographic method) or 10 to 20 ng/mL (using an immunoassay).
Calcineurin Inhibitors (CNI) Continuation
n=210 participants at risk
Calcineurin Inhibitors administered per local practice to attain target trough levels of 3 to 10 ng/mL (tacrolimus) or 50 to 250 ng/mL (cyclosporin A), respectively.
General disorders
Abdominal pain
2.6%
10/389
1.9%
4/210
General disorders
Abdominal syndrome acute
0.26%
1/389
0.48%
1/210
General disorders
Abscess
1.3%
5/389
0.00%
0/210
General disorders
Accidental injury
1.5%
6/389
1.4%
3/210
General disorders
Accidental overdose
0.77%
3/389
0.00%
0/210
General disorders
Adenoma
0.26%
1/389
0.00%
0/210
General disorders
Allergic reaction
0.26%
1/389
0.00%
0/210
General disorders
Ascites
0.26%
1/389
0.00%
0/210
General disorders
Asthenia
0.51%
2/389
0.95%
2/210
General disorders
Back pain
0.77%
3/389
0.00%
0/210
General disorders
Carcinoma
0.51%
2/389
0.00%
0/210
General disorders
Cellulitis
1.5%
6/389
1.4%
3/210
General disorders
Chest pain
1.0%
4/389
1.4%
3/210
General disorders
Chills
0.51%
2/389
1.4%
3/210
General disorders
Death
0.26%
1/389
0.00%
0/210
General disorders
Diarrhea infectious
0.26%
1/389
0.00%
0/210
General disorders
Face edema
0.26%
1/389
0.00%
0/210
General disorders
Fever
4.1%
16/389
3.8%
8/210
General disorders
Flu syndrome
0.26%
1/389
0.00%
0/210
General disorders
Headache
0.51%
2/389
0.00%
0/210
General disorders
Hernia
2.8%
11/389
1.4%
3/210
General disorders
Infection
2.6%
10/389
0.95%
2/210
General disorders
Medication error
0.26%
1/389
0.00%
0/210
General disorders
Neck pain
0.26%
1/389
0.00%
0/210
General disorders
Neoplasm
0.77%
3/389
0.00%
0/210
General disorders
Overdose
0.77%
3/389
0.00%
0/210
General disorders
Pain
1.0%
4/389
0.00%
0/210
General disorders
Sepsis
2.3%
9/389
1.4%
3/210
General disorders
Septic shock
0.26%
1/389
0.00%
0/210
General disorders
Transplant rejection
0.26%
1/389
0.48%
1/210
Cardiac disorders
Angina pectoris
0.77%
3/389
0.48%
1/210
Vascular disorders
Aortic stenosis
0.26%
1/389
0.00%
0/210
Cardiac disorders
Arterial anomaly
0.26%
1/389
0.48%
1/210
Vascular disorders
Arterial thrombosis
0.51%
2/389
0.00%
0/210
Cardiac disorders
Atrial fibrillation
0.26%
1/389
0.48%
1/210
Cardiac disorders
Atrial flutter
0.26%
1/389
0.00%
0/210
Cardiac disorders
AV block
0.26%
1/389
0.00%
0/210
Cardiac disorders
AV block complete
0.26%
1/389
0.48%
1/210
Cardiac disorders
Cardiomegaly
0.00%
0/389
0.48%
1/210
Cardiac disorders
Cardiomyopathy
0.26%
1/389
0.00%
0/210
Cardiac disorders
Cardiovascular disorder
0.77%
3/389
0.00%
0/210
Cardiac disorders
Cerebral ischemia
0.00%
0/389
0.48%
1/210
Vascular disorders
Cerebrovascular accident
0.26%
1/389
2.9%
6/210
Cardiac disorders
Coronary occlusion
0.26%
1/389
0.48%
1/210
Vascular disorders
Deep vein thrombosis
0.00%
0/389
0.48%
1/210
Cardiac disorders
Heart failure
1.0%
4/389
0.48%
1/210
Vascular disorders
Hemorrhage
0.77%
3/389
0.48%
1/210
Vascular disorders
Hypertension
0.51%
2/389
0.48%
1/210
Vascular disorders
Hypotension
0.26%
1/389
0.00%
0/210
Cardiac disorders
Left heart failure
0.26%
1/389
0.00%
0/210
Vascular disorders
Mesenteric venous occlusion
0.26%
1/389
0.00%
0/210
Cardiac disorders
Myocardial infarct
0.00%
0/389
0.48%
1/210
Cardiac disorders
Myocardial ischemia
0.51%
2/389
0.00%
0/210
Cardiac disorders
Pericardial effusion
0.26%
1/389
0.00%
0/210
Cardiac disorders
Pericarditis
0.26%
1/389
0.48%
1/210
Vascular disorders
Peripheral vascular disorder
0.26%
1/389
0.00%
0/210
Vascular disorders
Postural hypotension
0.26%
1/389
0.00%
0/210
Vascular disorders
Pulmonary embolus
0.00%
0/389
0.95%
2/210
Vascular disorders
Pulmonary hypertension
0.26%
1/389
0.00%
0/210
Cardiac disorders
Shock
0.26%
1/389
0.00%
0/210
Cardiac disorders
Sick sinus syndrome
0.26%
1/389
0.00%
0/210
Cardiac disorders
Supraventricular tachycardia
0.00%
0/389
0.48%
1/210
Cardiac disorders
Syncope
0.77%
3/389
0.48%
1/210
Cardiac disorders
Tachycardia
0.00%
0/389
0.48%
1/210
Vascular disorders
Vascular disorder
0.00%
0/389
0.48%
1/210
Gastrointestinal disorders
Carcinoma of the mouth
0.00%
0/389
0.48%
1/210
Gastrointestinal disorders
Cholangitis
1.3%
5/389
0.95%
2/210
Gastrointestinal disorders
Cholelithiasis
0.51%
2/389
0.00%
0/210
Gastrointestinal disorders
Colitis
0.51%
2/389
0.48%
1/210
Gastrointestinal disorders
Constipation
0.26%
1/389
0.00%
0/210
Gastrointestinal disorders
Diarrhea
4.1%
16/389
2.4%
5/210
Gastrointestinal disorders
Enteritis
0.00%
0/389
0.48%
1/210
Gastrointestinal disorders
Esophageal stenosis
0.26%
1/389
0.00%
0/210
Gastrointestinal disorders
Gamma glutamyl transpeptidase increased
0.77%
3/389
0.00%
0/210
Gastrointestinal disorders
Gastroenteritis
2.3%
9/389
1.9%
4/210
Gastrointestinal disorders
Gastrointestinal carcinoma
1.0%
4/389
1.9%
4/210
Gastrointestinal disorders
Gastrointestinal disorder
2.1%
8/389
0.48%
1/210
Gastrointestinal disorders
Gastrointestinal hemorrhage
1.0%
4/389
0.95%
2/210
Gastrointestinal disorders
Hepatic neoplasia
0.77%
3/389
0.95%
2/210
Gastrointestinal disorders
Hepatitis
0.51%
2/389
0.48%
1/210
Gastrointestinal disorders
Ileitis
0.00%
0/389
0.48%
1/210
Gastrointestinal disorders
Ileus
0.77%
3/389
0.48%
1/210
Gastrointestinal disorders
Intestinal obstruction
0.51%
2/389
0.48%
1/210
Gastrointestinal disorders
Jaundice
0.00%
0/389
0.48%
1/210
Gastrointestinal disorders
Liver damage
0.26%
1/389
0.48%
1/210
Gastrointestinal disorders
Liver fatty deposit
0.26%
1/389
0.00%
0/210
Gastrointestinal disorders
Liver function tests abnormal
3.9%
15/389
1.4%
3/210
Gastrointestinal disorders
Melena
0.00%
0/389
0.48%
1/210
Gastrointestinal disorders
Nausea
1.5%
6/389
0.48%
1/210
Gastrointestinal disorders
Nausea and vomiting
0.00%
0/389
0.48%
1/210
Gastrointestinal disorders
Pancreatitis
0.51%
2/389
0.00%
0/210
Gastrointestinal disorders
Peridontal abcess
0.26%
1/389
0.00%
0/210
Gastrointestinal disorders
Rectal disorder
0.26%
1/389
0.95%
2/210
Endocrine disorders
Diabetes mellitus
0.77%
3/389
0.95%
2/210
Endocrine disorders
Thyroid disorder
0.00%
0/389
0.48%
1/210
Blood and lymphatic system disorders
Anemia
3.1%
12/389
1.9%
4/210
Blood and lymphatic system disorders
Aplastic anema
0.00%
0/389
0.48%
1/210
Blood and lymphatic system disorders
Coagulation disorder
0.00%
0/389
0.48%
1/210
Blood and lymphatic system disorders
International normalized ratio increased
0.26%
1/389
0.00%
0/210
Blood and lymphatic system disorders
Leukopenia
0.26%
1/389
0.00%
0/210
Blood and lymphatic system disorders
Lymphadenopathy
0.51%
2/389
0.00%
0/210
Blood and lymphatic system disorders
Lymphagitis
0.26%
1/389
0.00%
0/210
Blood and lymphatic system disorders
Microcytic anemia
0.26%
1/389
0.00%
0/210
Blood and lymphatic system disorders
Pancytopenia
0.26%
1/389
0.48%
1/210
Metabolism and nutrition disorders
Acidosis
0.26%
1/389
0.00%
0/210
Metabolism and nutrition disorders
Alkaline phosphotase increased
1.8%
7/389
0.00%
0/210
Metabolism and nutrition disorders
Bilirubinemia
0.00%
0/389
0.48%
1/210
Metabolism and nutrition disorders
BUN increased
0.51%
2/389
0.00%
0/210
Metabolism and nutrition disorders
Creatinine increased
1.3%
5/389
0.95%
2/210
Metabolism and nutrition disorders
Dehydration
1.0%
4/389
1.4%
3/210
Metabolism and nutrition disorders
Diabetic ketoacidosis
0.26%
1/389
0.00%
0/210
Metabolism and nutrition disorders
Electrolyte abnormality
0.26%
1/389
0.00%
0/210
Metabolism and nutrition disorders
Gout
0.00%
0/389
0.48%
1/210
Metabolism and nutrition disorders
Healing abnormal
1.3%
5/389
0.95%
2/210
Metabolism and nutrition disorders
Hyperglycemia
0.51%
2/389
0.48%
1/210
Metabolism and nutrition disorders
Hyperkalemia
0.00%
0/389
0.48%
1/210
Metabolism and nutrition disorders
Hyperlipemia
0.26%
1/389
0.00%
0/210
Metabolism and nutrition disorders
Hypocalcemia
0.26%
1/389
0.00%
0/210
Metabolism and nutrition disorders
Hypoglycemia
0.51%
2/389
0.00%
0/210
Metabolism and nutrition disorders
Hypokalemia
0.77%
3/389
0.00%
0/210
Metabolism and nutrition disorders
Hyponatremia
0.00%
0/389
0.48%
1/210
Metabolism and nutrition disorders
Peripheral edema
1.0%
4/389
0.00%
0/210
Metabolism and nutrition disorders
SGOT increased
1.5%
6/389
0.95%
2/210
Metabolism and nutrition disorders
SGPT increased
1.3%
5/389
0.95%
2/210
Metabolism and nutrition disorders
Weight gain
0.00%
0/389
0.48%
1/210
Metabolism and nutrition disorders
Weight loss
0.26%
1/389
0.48%
1/210
Musculoskeletal and connective tissue disorders
Arthralgia
0.77%
3/389
0.95%
2/210
Musculoskeletal and connective tissue disorders
Arthritis
0.51%
2/389
0.00%
0/210
Musculoskeletal and connective tissue disorders
Arthrosis
0.51%
2/389
0.95%
2/210
Musculoskeletal and connective tissue disorders
Bone necrosis
0.26%
1/389
0.00%
0/210
Musculoskeletal and connective tissue disorders
Bursitis
0.26%
1/389
0.00%
0/210
Musculoskeletal and connective tissue disorders
Musculoskeletal anomaly
0.26%
1/389
0.00%
0/210
Musculoskeletal and connective tissue disorders
Osteomyelitis
0.00%
0/389
0.48%
1/210
Nervous system disorders
Alcoholism
0.26%
1/389
0.00%
0/210
Nervous system disorders
Aphasia
0.00%
0/389
0.48%
1/210
Nervous system disorders
CNS neoplasia
0.00%
0/389
0.48%
1/210
Nervous system disorders
Convulsion
0.51%
2/389
0.48%
1/210
Nervous system disorders
Depression
0.26%
1/389
0.48%
1/210
Nervous system disorders
Dizziness
0.26%
1/389
0.48%
1/210
Nervous system disorders
Dysarthria
0.00%
0/389
0.48%
1/210
Nervous system disorders
Hemiplegia
0.00%
0/389
0.48%
1/210
Nervous system disorders
Hypesthesia
0.26%
1/389
0.00%
0/210
Nervous system disorders
Subdural hematoma
0.26%
1/389
0.00%
0/210
Respiratory, thoracic and mediastinal disorders
Bronchitis
0.00%
0/389
0.95%
2/210
Respiratory, thoracic and mediastinal disorders
Carcinoma of lung
0.77%
3/389
0.95%
2/210
Respiratory, thoracic and mediastinal disorders
Cough increased
0.77%
3/389
0.48%
1/210
Respiratory, thoracic and mediastinal disorders
Dyspnea
1.8%
7/389
0.48%
1/210
Respiratory, thoracic and mediastinal disorders
Hemoptysis
0.26%
1/389
0.48%
1/210
Respiratory, thoracic and mediastinal disorders
Hemothorax
0.26%
1/389
0.00%
0/210
Respiratory, thoracic and mediastinal disorders
Interstitial pneumonia
0.26%
1/389
0.00%
0/210
Respiratory, thoracic and mediastinal disorders
Laryngitis
0.26%
1/389
0.00%
0/210
Respiratory, thoracic and mediastinal disorders
Lung disorder
0.51%
2/389
0.00%
0/210
Respiratory, thoracic and mediastinal disorders
Lung edema
0.26%
1/389
0.00%
0/210
Respiratory, thoracic and mediastinal disorders
Lung hemorrhage
0.26%
1/389
0.00%
0/210
Respiratory, thoracic and mediastinal disorders
Lung infiltration nos
0.26%
1/389
0.00%
0/210
Respiratory, thoracic and mediastinal disorders
Pharyngitis
0.51%
2/389
0.00%
0/210
Respiratory, thoracic and mediastinal disorders
Pleural effusion
0.51%
2/389
0.00%
0/210
Respiratory, thoracic and mediastinal disorders
Pneumonia
4.4%
17/389
1.9%
4/210
Respiratory, thoracic and mediastinal disorders
Pneumonitis
0.51%
2/389
0.00%
0/210
Respiratory, thoracic and mediastinal disorders
Pneumothorax
0.26%
1/389
0.00%
0/210
Respiratory, thoracic and mediastinal disorders
Sinusitis
0.26%
1/389
0.00%
0/210
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
1.3%
5/389
0.48%
1/210
Skin and subcutaneous tissue disorders
Herpes simplex
0.26%
1/389
0.00%
0/210
Skin and subcutaneous tissue disorders
Herpes zoster
0.26%
1/389
0.48%
1/210
Skin and subcutaneous tissue disorders
Maculopapular rash
0.26%
1/389
0.00%
0/210
Skin and subcutaneous tissue disorders
Purpuric rash
0.00%
0/389
0.48%
1/210
Skin and subcutaneous tissue disorders
Rash
0.77%
3/389
0.48%
1/210
Skin and subcutaneous tissue disorders
Skin carcinoma
3.6%
14/389
9.0%
19/210
Skin and subcutaneous tissue disorders
Skin hypertrophy
0.26%
1/389
0.00%
0/210
Skin and subcutaneous tissue disorders
Skin melanoma
0.26%
1/389
1.4%
3/210
Skin and subcutaneous tissue disorders
Skin ulcer
0.26%
1/389
0.00%
0/210
Eye disorders
Cataract specified
0.26%
1/389
0.48%
1/210
Eye disorders
Eye hemorrhage
0.26%
1/389
0.00%
0/210
Eye disorders
Glaucoma
0.26%
1/389
0.00%
0/210
Eye disorders
Retinal detachment
0.26%
1/389
0.00%
0/210
Eye disorders
Retinal disorder
0.26%
1/389
0.00%
0/210
Renal and urinary disorders
Acute kidney failure
1.8%
7/389
0.95%
2/210
Renal and urinary disorders
Albuminuria
0.26%
1/389
0.00%
0/210
Reproductive system and breast disorders
Breast neoplasm
0.00%
0/389
0.48%
1/210
Renal and urinary disorders
Dysuria
0.26%
1/389
0.48%
1/210
Reproductive system and breast disorders
Fallopian tube disorder
0.26%
1/389
0.00%
0/210
Renal and urinary disorders
Hematuria
0.00%
0/389
0.48%
1/210
Renal and urinary disorders
Hydronephrosis
0.26%
1/389
0.48%
1/210
Renal and urinary disorders
Kidney calculus
0.77%
3/389
0.48%
1/210
Renal and urinary disorders
Kidney failure
1.8%
7/389
0.48%
1/210
Renal and urinary disorders
Kidney function abnormal
1.5%
6/389
0.48%
1/210
Renal and urinary disorders
Nephritis
0.26%
1/389
0.00%
0/210
Renal and urinary disorders
Nephrosclerosis
0.51%
2/389
0.00%
0/210
Renal and urinary disorders
Nephrosis
0.26%
1/389
0.00%
0/210
Reproductive system and breast disorders
Ovarian cyst
0.77%
3/389
0.00%
0/210
Reproductive system and breast disorders
Ovarian disorder
0.00%
0/389
0.48%
1/210
Renal and urinary disorders
Polyuria
0.26%
1/389
0.00%
0/210
Reproductive system and breast disorders
Prostatic carcinoma
0.77%
3/389
0.00%
0/210
Reproductive system and breast disorders
Prostatic disorder
0.00%
0/389
0.48%
1/210
Renal and urinary disorders
Pyelonephritis
0.26%
1/389
0.00%
0/210
Reproductive system and breast disorders
Unintended pregnancy
0.00%
0/389
0.48%
1/210
Renal and urinary disorders
Uremia
0.51%
2/389
0.48%
1/210
Renal and urinary disorders
Urinary tract disorder
0.00%
0/389
0.48%
1/210
Renal and urinary disorders
Urinary tract infection
1.8%
7/389
1.4%
3/210
Renal and urinary disorders
Urine abnormality
0.26%
1/389
0.00%
0/210
Renal and urinary disorders
Urolithiasis
0.26%
1/389
0.00%
0/210
General disorders
Device malfunction
0.26%
1/389
0.48%
1/210
General disorders
Local reaction to procedure
3.3%
13/389
1.4%
3/210
General disorders
Surgical procedure
0.26%
1/389
0.00%
0/210
Gastrointestinal disorders
Rectal hemorrhage
0.00%
0/389
0.48%
1/210
Gastrointestinal disorders
Sclerosing cholangitis
0.26%
1/389
0.00%
0/210
Gastrointestinal disorders
Stomatitis
0.26%
1/389
0.00%
0/210
Gastrointestinal disorders
Stools abnormal
0.26%
1/389
0.00%
0/210
Gastrointestinal disorders
Ulcerative colitis
0.26%
1/389
0.95%
2/210
Gastrointestinal disorders
Vomiting
2.6%
10/389
0.95%
2/210

Other adverse events

Other adverse events
Measure
Sirolimus (SRL) Conversion
n=389 participants at risk
Sirolimus was administered once daily. A loading dose of sirolimus, 10 to 15 mg, was administered in divided doses on day 1: the first dose was given after collection of the sirolimus trough level and a minimum of 4 hours following the last dose of CNI, and the second dose approximately 12 hours after the first dose. On days 2 through 6, sirolimus was administered in a dose of 3 to 5 mg/day. For the remaining study period, day 7 through month 72, appropriate daily doses of sirolimus were administered to attain the recommended trough concentrations of 8 to 16 ng/mL (using a chromatographic method) or 10 to 20 ng/mL (using an immunoassay).
Calcineurin Inhibitors (CNI) Continuation
n=210 participants at risk
Calcineurin Inhibitors administered per local practice to attain target trough levels of 3 to 10 ng/mL (tacrolimus) or 50 to 250 ng/mL (cyclosporin A), respectively.
General disorders
Abdominal pain
18.0%
70/389
14.3%
30/210
General disorders
Accidental injury
17.2%
67/389
15.2%
32/210
General disorders
Asthenia
20.3%
79/389
13.3%
28/210
General disorders
Back pain
10.8%
42/389
12.9%
27/210
General disorders
Chest pain
8.0%
31/389
8.6%
18/210
General disorders
Face edema
5.7%
22/389
1.9%
4/210
General disorders
Fever
20.3%
79/389
12.4%
26/210
General disorders
Flu syndrome
5.7%
22/389
3.3%
7/210
General disorders
Headache
21.6%
84/389
11.0%
23/210
General disorders
Hernia
6.4%
25/389
4.8%
10/210
General disorders
Pain
18.3%
71/389
18.6%
39/210
Cardiac disorders
Hypertension
16.7%
65/389
19.0%
40/210
Gastrointestinal disorders
Anorexia
6.4%
25/389
2.4%
5/210
Gastrointestinal disorders
Aphthous stomatitis
8.7%
34/389
0.95%
2/210
Gastrointestinal disorders
Constipation
9.3%
36/389
9.5%
20/210
Gastrointestinal disorders
Diarrhea
35.0%
136/389
18.1%
38/210
Gastrointestinal disorders
Dyspepsia
4.4%
17/389
5.2%
11/210
Gastrointestinal disorders
Gastrointestinal disorder
6.7%
26/389
4.8%
10/210
Gastrointestinal disorders
Liver function tests abnormal
15.2%
59/389
11.9%
25/210
Gastrointestinal disorders
Mouth ulceration
11.3%
44/389
0.95%
2/210
Gastrointestinal disorders
Nausea
13.1%
51/389
9.0%
19/210
Gastrointestinal disorders
Stomatitis
26.5%
103/389
1.9%
4/210
Gastrointestinal disorders
Vomiting
9.0%
35/389
8.1%
17/210
Endocrine disorders
Diabetes mellitus
6.4%
25/389
4.3%
9/210
Blood and lymphatic system disorders
Anemia
24.2%
94/389
9.0%
19/210
Blood and lymphatic system disorders
Leukopenia
14.1%
55/389
4.8%
10/210
Blood and lymphatic system disorders
Thrombocytopenia
14.9%
58/389
3.8%
8/210
Metabolism and nutrition disorders
Alkaline phosphatase increased
8.2%
32/389
4.8%
10/210
Metabolism and nutrition disorders
BUN increased
3.1%
12/389
6.2%
13/210
Metabolism and nutrition disorders
Creatinine increased
6.2%
24/389
12.4%
26/210
Metabolism and nutrition disorders
Hypercholesteremia
28.3%
110/389
4.3%
9/210
Metabolism and nutrition disorders
Hyperglycemia
10.0%
39/389
10.5%
22/210
Metabolism and nutrition disorders
Hyperkalemia
2.8%
11/389
8.1%
17/210
Metabolism and nutrition disorders
Hyperlipemia
40.9%
159/389
9.5%
20/210
Metabolism and nutrition disorders
Hyperuricemia
2.6%
10/389
7.6%
16/210
Metabolism and nutrition disorders
Hypokalemia
5.9%
23/389
2.4%
5/210
Metabolism and nutrition disorders
Lactic dehydrogenase increased
5.1%
20/389
1.4%
3/210
Metabolism and nutrition disorders
Peripheral edema
32.6%
127/389
13.8%
29/210
Metabolism and nutrition disorders
SGOT increased
9.5%
37/389
5.7%
12/210
Metabolism and nutrition disorders
SGPT increased
10.3%
40/389
4.3%
9/210
Metabolism and nutrition disorders
Weight loss
6.7%
26/389
2.9%
6/210
Musculoskeletal and connective tissue disorders
Arthralgia
14.7%
57/389
16.7%
35/210
Musculoskeletal and connective tissue disorders
Leg cramps
1.3%
5/389
5.7%
12/210
Nervous system disorders
Depression
4.1%
16/389
6.2%
13/210
Nervous system disorders
Dizziness
9.3%
36/389
7.1%
15/210
Nervous system disorders
Insomnia
6.9%
27/389
5.2%
11/210
Nervous system disorders
Paresthesia
5.1%
20/389
1.9%
4/210
Respiratory, thoracic and mediastinal disorders
Cough increased
17.0%
66/389
13.3%
28/210
Respiratory, thoracic and mediastinal disorders
Dyspnea
9.3%
36/389
6.2%
13/210
Respiratory, thoracic and mediastinal disorders
Pharyngitis
10.3%
40/389
6.7%
14/210
Respiratory, thoracic and mediastinal disorders
Rhinitis
9.0%
35/389
5.2%
11/210
Skin and subcutaneous tissue disorders
Acne
13.4%
52/389
1.9%
4/210
Skin and subcutaneous tissue disorders
Dry skin
8.2%
32/389
1.4%
3/210
Respiratory, thoracic and mediastinal disorders
Erythema
6.2%
24/389
1.4%
3/210
Respiratory, thoracic and mediastinal disorders
Pruritus
12.9%
50/389
6.7%
14/210
Skin and subcutaneous tissue disorders
Rash
28.5%
111/389
7.6%
16/210
Skin and subcutaneous tissue disorders
Skin disorder
7.2%
28/389
6.2%
13/210
Skin and subcutaneous tissue disorders
Skin hypertrophy
2.1%
8/389
5.7%
12/210
Renal and urinary disorders
Albuminuria
6.4%
25/389
2.4%
5/210
Renal and urinary disorders
Kidney function abnormal
6.2%
24/389
10.5%
22/210
Injury, poisoning and procedural complications
Local reaction to procedure
9.3%
36/389
7.6%
16/210
General disorders
Cellulitis
5.1%
20/389
3.3%
7/210
General disorders
Flu Syndrome
4.1%
16/389
7.1%
15/210
General disorders
Infection
24.9%
97/389
20.5%
43/210
Gastrointestinal disorders
Gastroenteritis
4.9%
19/389
5.7%
12/210
Respiratory, thoracic and mediastinal disorders
Bronchitis
6.4%
25/389
6.7%
14/210
Respiratory, thoracic and mediastinal disorders
Pneumonia
7.7%
30/389
4.3%
9/210
Respiratory, thoracic and mediastinal disorders
Sinusitis
6.9%
27/389
7.1%
15/210
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Infection
13.9%
54/389
17.1%
36/210
Skin and subcutaneous tissue disorders
Herpes Simplex
8.5%
33/389
1.4%
3/210
Renal and urinary disorders
Urinary Tract Infection
9.3%
36/389
10.0%
21/210
Skin and subcutaneous tissue disorders
Skin Carcinoma
3.6%
14/389
9.0%
19/210

Additional Information

U. S. Contact Center

Wyeth

Results disclosure agreements

  • Principal investigator is a sponsor employee The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
  • Publication restrictions are in place

Restriction type: OTHER