Trial Outcomes & Findings for Pharmacokinetics of Sirolimus and Tacrolimus in Liver Transplant Recipients With Tacrolimus Toxicity (NCT NCT01709136)

Results Overview

To evaluate early and late pharmacokinetics of Sirolimus (SRL) , and safety and efficacy of conversion from tacrolimus (TAC) to sirolimus in liver transplant recipients who have been stable for at least 3 months, and who have early nephrotoxicity and/or hypertension due to use of tacrolimus.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

3 participants

Primary outcome timeframe

1 year

Results posted on

2023-03-30

Participant Flow

Participant milestones

Participant milestones
Measure	Sirolimus Sirolimus: Single dose SRL pharmacokinetics and TAC steady state pharmacokinetics: This phase is applicable to both sets of patients: those with nephrotoxicity and those with hypertension. Patients will receive a single dose of SRL of 2 mg/m2. Blood sampling will be performed over a 24 hour stay in the Children's Hospital of Pittsburgh Pediatric Clinical and Translational Research Center (PCTRC) - See more at: http://www.chp.edu/research/our-facilities/pctrc, and the sampling for 48 hour and 72 hour PK studies can be done at the outpatient lab. This phase can either be performed immediately after the 12-hour iothalamate Glomerular Filtration Rate (GFR) evaluation, or a few days later at the convenience of the subject.
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics of Sirolimus and Tacrolimus in Liver Transplant Recipients With Tacrolimus Toxicity

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sirolimus n=3 Participants Sirolimus: Single dose SRL pharmacokinetics and TAC steady state pharmacokinetics: This phase is applicable to both sets of patients: those with nephrotoxicity and those with hypertension. Patients will receive a single dose of SRL of 2 mg/m2. Blood sampling will be performed over a 24 hour stay in the PCTRC , and the sampling for 48 hour and 72 hour PK studies can be done at the outpatient lab. This phase can either be performed immediately after the 12-hour iothalamate GFR evaluation, or a few days later at the convenience of the subject.
Age, Categorical <=18 years	3 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Population: Three pharmacokinetics (PK) profiles were performed, one in each of three patients who were enrolled. However, due to FDA blackbox warnings (6/11/2009) about Sirolimus in liver transplant recipients be circumspect (risk of thrombosis and death), the study was terminated early and data analysis was not able to be completed.

To evaluate early and late pharmacokinetics of Sirolimus (SRL) , and safety and efficacy of conversion from tacrolimus (TAC) to sirolimus in liver transplant recipients who have been stable for at least 3 months, and who have early nephrotoxicity and/or hypertension due to use of tacrolimus.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Population: We were able to preform 3 pharmacokinetics (PK) profiles, one in each of three patients enrolled. However, due to emerging data and blackbox warnings from FDA suggesting that use of Sirolimus in liver transplant recipients be circumspect (risk of thrombosis and death), the study was terminated early and data analysis was not able to be completed.

pharmacokinetics (PK) of SRL after a single dose and after steady state has been achieved; and the pharmacokinetics of tacrolimus once at steady state

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Population: Due to FDA blackbox warnings (6/11/09) about Sirolimus in liver transplant recipients (risk of thrombosis and death), the study was terminated early. Due to the early termination of this study and small number of subjects enrolled (3), data analysis was not able to be completed.

Whether Sirolimus can substitute Tacrolimus in the stable post-transplant state, without compromising allograft function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

Population: Due to FDA blackbox warnings from FDA (6/11/2009) about Sirolimus in liver transplant recipients (risk of thrombosis and death), the study was terminated early and data analysis was not able to be completed.

Whether SRL can prevent or minimize progression of selected TAC-related side-effects such as renal dysfunction as measured by clearance of iothalamate (Glomerular filtration rate \< 80 mL/min/1.73 m2) and hypertension (blood pressure \> 140/90 mm Hg)

Outcome measures

Outcome data not reported

Adverse Events

Sirolimus

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Rakesh Sindhi, MD

Children's Hospital of Pittsburgh

Phone: 412-692-6110

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place