Trial Outcomes & Findings for A Randomized Controlled Clinical Trial of Thymoglobulin® After Liver Transplantation (NCT NCT02544113)

NCT ID: NCT02544113

Last Updated: 2021-05-06

Results Overview

Change in serum creatinine from baseline to 30 days post-transplant. Higher values are associated with worse outcomes, and values greater than 0.3 mg/dL are suggestive of acute kidney injury.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 110 participants
• Primary outcome timeframe: 30 days post-transplant
• Results posted on: 2021-05-06

Participant Flow

Participant milestones

Measure	Thymo Subjects randomized to the (Delay CNI) group will be treated with Thymoglobulin® (total dose of 4.5 mg/kg) administered in three doses; (each dose being 1.5 mg/kg - administered Day 0 \[after transplant\], Day 2, and Day 4 post transplant), along with CNI delay for 10 days. CNI will be initiated on postoperative (post-transplant) Day 10. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center. Thymoglobulin: Treatment with thymoglobulin and delayed CNI post OLT	Control Subjects randomized to the (Early CNI) group (Control group) will receive no antibody therapy for induction and will start CNI therapy on postoperative (post-transplant) Day 2. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center. Placebo: Normal transplant immunosuppression
Overall Study STARTED	55	55
Overall Study COMPLETED	52	51
Overall Study NOT COMPLETED	3	4

Reasons for withdrawal

Measure	Thymo Subjects randomized to the (Delay CNI) group will be treated with Thymoglobulin® (total dose of 4.5 mg/kg) administered in three doses; (each dose being 1.5 mg/kg - administered Day 0 \[after transplant\], Day 2, and Day 4 post transplant), along with CNI delay for 10 days. CNI will be initiated on postoperative (post-transplant) Day 10. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center. Thymoglobulin: Treatment with thymoglobulin and delayed CNI post OLT	Control Subjects randomized to the (Early CNI) group (Control group) will receive no antibody therapy for induction and will start CNI therapy on postoperative (post-transplant) Day 2. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center. Placebo: Normal transplant immunosuppression
Overall Study Death	3	4

Baseline Characteristics

A Randomized Controlled Clinical Trial of Thymoglobulin® After Liver Transplantation

Baseline characteristics by cohort

Measure	Thymo n=55 Participants Subjects randomized to the (Delay CNI) group will be treated with Thymoglobulin® (total dose of 4.5 mg/kg) administered in three doses; (each dose being 1.5 mg/kg - administered Day 0 \[after transplant\], Day 2, and Day 4 post transplant), along with CNI delay for 10 days. CNI will be initiated on postoperative (post-transplant) Day 10. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center. Thymoglobulin: Treatment with thymoglobulin and delayed CNI post OLT	Control n=55 Participants Subjects randomized to the (Early CNI) group (Control group) will receive no antibody therapy for induction and will start CNI therapy on postoperative (post-transplant) Day 2. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center. Placebo: Normal transplant immunosuppression	Total n=110 Participants Total of all reporting groups
Age, Continuous	57.1 years STANDARD_DEVIATION 12.2 • n=5 Participants	59.8 years STANDARD_DEVIATION 12.1 • n=7 Participants	58.5 years STANDARD_DEVIATION 12.2 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	22 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants	33 Participants n=7 Participants	73 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	52 Participants n=5 Participants	49 Participants n=7 Participants	101 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 30 days post-transplant

Population: Analysis was performed on a complete-case basis. Outcome measure data was not available for all enrolled subjects.

Change in serum creatinine from baseline to 30 days post-transplant. Higher values are associated with worse outcomes, and values greater than 0.3 mg/dL are suggestive of acute kidney injury.

Outcome measures

Measure	Thymo n=43 Participants Subjects randomized to the (Delay CNI) group will be treated with Thymoglobulin® (total dose of 4.5 mg/kg) administered in three doses; (each dose being 1.5 mg/kg - administered Day 0 \[after transplant\], Day 2, and Day 4 post transplant), along with CNI delay for 10 days. CNI will be initiated on postoperative (post-transplant) Day 10. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center. Thymoglobulin: Treatment with thymoglobulin and delayed CNI post OLT	Control n=52 Participants Subjects randomized to the (Early CNI) group (Control group) will receive no antibody therapy for induction and will start CNI therapy on postoperative (post-transplant) Day 2. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center. Placebo: Normal transplant immunosuppression
The Incidence of Acute Kidney Injury (AKI) as Assessed by Change in Serum Creatinine From Baseline to 30 Days Post-transplant	.01 mg/dL Standard Deviation 0.53	.06 mg/dL Standard Deviation 0.28

SECONDARY outcome

Timeframe: 30 days post OLT

The number of participants experiencing acute cellular rejection, as determined by biopsy.

Outcome measures

Measure	Thymo n=55 Participants Subjects randomized to the (Delay CNI) group will be treated with Thymoglobulin® (total dose of 4.5 mg/kg) administered in three doses; (each dose being 1.5 mg/kg - administered Day 0 \[after transplant\], Day 2, and Day 4 post transplant), along with CNI delay for 10 days. CNI will be initiated on postoperative (post-transplant) Day 10. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center. Thymoglobulin: Treatment with thymoglobulin and delayed CNI post OLT	Control n=55 Participants Subjects randomized to the (Early CNI) group (Control group) will receive no antibody therapy for induction and will start CNI therapy on postoperative (post-transplant) Day 2. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center. Placebo: Normal transplant immunosuppression
Number of Participants Experiencing Acute Cellular Rejection	9 Participants	7 Participants

SECONDARY outcome

Timeframe: 6 months post OLT

Number of participants who did not require retransplantation

Outcome measures

Measure	Thymo n=55 Participants Subjects randomized to the (Delay CNI) group will be treated with Thymoglobulin® (total dose of 4.5 mg/kg) administered in three doses; (each dose being 1.5 mg/kg - administered Day 0 \[after transplant\], Day 2, and Day 4 post transplant), along with CNI delay for 10 days. CNI will be initiated on postoperative (post-transplant) Day 10. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center. Thymoglobulin: Treatment with thymoglobulin and delayed CNI post OLT	Control n=55 Participants Subjects randomized to the (Early CNI) group (Control group) will receive no antibody therapy for induction and will start CNI therapy on postoperative (post-transplant) Day 2. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center. Placebo: Normal transplant immunosuppression
Graft Survival	55 Participants	55 Participants

Adverse Events

Thymo

Serious events: 13 serious events

Other events: 0 other events

Deaths: 3 deaths

Control

Serious events: 13 serious events

Other events: 0 other events

Deaths: 4 deaths

Serious adverse events

Measure	Thymo n=55 participants at risk Subjects randomized to the (Delay CNI) group will be treated with Thymoglobulin® (total dose of 4.5 mg/kg) administered in three doses; (each dose being 1.5 mg/kg - administered Day 0 \[after transplant\], Day 2, and Day 4 post transplant), along with CNI delay for 10 days. CNI will be initiated on postoperative (post-transplant) Day 10. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center. Thymoglobulin: Treatment with thymoglobulin and delayed CNI post OLT	Control n=55 participants at risk Subjects randomized to the (Early CNI) group (Control group) will receive no antibody therapy for induction and will start CNI therapy on postoperative (post-transplant) Day 2. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center. Placebo: Normal transplant immunosuppression
Infections and infestations Infection	14.5% 8/55 • Number of events 9 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits	14.5% 8/55 • Number of events 11 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits
Gastrointestinal disorders Bowel Obstruction	1.8% 1/55 • Number of events 1 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits	1.8% 1/55 • Number of events 1 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits
Respiratory, thoracic and mediastinal disorders Respiratory Insufficiency	0.00% 0/55 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits	5.5% 3/55 • Number of events 4 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits
Blood and lymphatic system disorders Hypertension	1.8% 1/55 • Number of events 1 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits	1.8% 1/55 • Number of events 1 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits
Blood and lymphatic system disorders Hypotension	0.00% 0/55 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits	5.5% 3/55 • Number of events 3 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits
Hepatobiliary disorders Hepatic Artery Thrombosis	1.8% 1/55 • Number of events 3 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits	1.8% 1/55 • Number of events 1 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits
Hepatobiliary disorders Portal Vein Stenosis	0.00% 0/55 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits	1.8% 1/55 • Number of events 1 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits
Nervous system disorders Seizure	0.00% 0/55 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits	1.8% 1/55 • Number of events 1 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits
Hepatobiliary disorders Abnormal Liver Function Tests	9.1% 5/55 • Number of events 5 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits	0.00% 0/55 • Adverse event data was collected over 12 months Participants were assessed for adverse events at regular study visits

Other adverse events

Adverse event data not reported

Additional Information

Dr. Bijan Eghtesad

Cleveland Clinic

Phone: 216 444-9898

Email: eghtesb@ccf.org

Results disclosure agreements

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