HypertensionPhase 2/3SirolimusNCT01709136

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

A Phase 2/3 study testing Sirolimus in people with Hypertension, run by University of Pittsburgh.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial summary

Pharmacokinetics of Tacrolimus and Sirolimus alone and in combination in liver transplant recipients. Read more about this study

Who is it for?: Ages 1 year to 18 years
Conditions the study is for: Hypertension
What is being tested?: Sirolimus
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3 participants
Where: No sites listed yet
Study dates: Dec 2005to Jan 2010
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 year to 18 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Recipients of primary liver (cadaver/liver, whole/segmental) transplants 5- 30 years old.
Rejection-free post-transplant course for at least 3 months
Renal dysfunction (15% decrease in age-adjusted calculated creatinine clearance)
Hypertension requiring anti-hypertensive mediations.
Informed consent.
Weight ≥15 kg.

Who cannot join

Rejection or infections within 3 months of enrollment.
Intent to continue TAC
Active participation in ongoing studies of immunosuppressive agents.
Lack of informed consent.
Pregnant or breast feeding
HIV positive

About this study

Official title: Pharmacokinetics of Sirolimus and Tacrolimus in Liver Transplant Recipients With Early Nephrotoxicity and/or Hypertension Due to Tacrolimus

Pharmacokinetics of Tacrolimus and Sirolimus alone and in combination in liver transplant recipients.

Read the detailed description

Liver transplant patients receiving tacrolimus, and who experience side effects such as hypertension and renal dysfunction, will be converted to sirolimus with low-dose tacrolimus, or Tacrolimus withdrawal. This study will evaluate allograft function by serial clinical lab testing, the pharmacokinetics of sirolimus and tacrolimus, the glomerular filtration rate (GFR) and the potential side effect of sirolimus, such as marrow suppression and hyperlipidemia. Two pharmacokinetic evaluations are planned: once around the third post-transplant month and another one at about 12 months. Expected outcomes are, a better understanding of sirolimus pharmacokinetic parameters over time in pediatric/adult liver recipients and early efficacy and safety data of the sirolimus as a non-nephrotoxic alternative to tacrolimus.

Conditions: Hypertension
Being tested: Sirolimus
Medical subject headings: Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SirolimusDrug
Also called Sirolimus (Rapamycin), Tacrolimus (FK506)
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's 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 GFR evaluation, or a few days later at the convenience of the subject.

Study groups in NCT01709136
Study group	Role	What they receive
Sirolimus	Experimental	Not described Receives: Drug: Sirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

Early and Late Pharmacokinetics of Sirolimus (SRL)
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.
Measured: 1 year

Secondary outcomes (3)

PK Parameters for Tacrolimus and Sirolimus
pharmacokinetics (PK) of SRL after a single dose and after steady state has been achieved; and the pharmacokinetics of tacrolimus once at steady state
Measured: 12 months
SRL Can Substitute TAC
Whether Sirolimus can substitute Tacrolimus in the stable post-transplant state, without compromising allograft function
Measured: 12 months
SRL Prevent TAC-related Side Effects
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)
Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2005Jan 2010

First posted17 Oct 2012 (estimated)
Study startDec 2005
Primary completionJan 2010
Study completionJan 2010

Why it stopped: Sirolimus usage discontinued since black box warning

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HypertensionStudies of the same condition, open and under way.
More trials run by University of PittsburghThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 3 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01709136
Sponsor's protocol ID: 07100379
Acronym: Sirolimus
Status last verified: Mar 2023
First submitted: 29 Jun 2010
Last updated: 30 Mar 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacokinetics of Sirolimus and Tacrolimus in Liver Transplant Recipients With Early Nephrotoxicity and/or Hypertension Due to Tacrolimus
ClinicalTrials.gov ID: NCT01709136
Acronym / sponsor ID: Sirolimus / 07100379
Conditions: Hypertension
Phase: Phase 2/3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Sirolimus usage discontinued since black box warning
Enrolment: 3 participants (actual)
Lead sponsor: University of PittsburghUniversity, hospital or other
Study start: Dec 2005
Primary completion: Jan 2010 (actual)
Study completion: Jan 2010 (actual)
First posted: 17 Oct 2012 (estimated)
Results: Posted 21 Apr 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Pharmacokinetics of Tacrolimus and Sirolimus alone and in combination in liver transplant recipients.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Sirolimus	Experimental	Drug: Sirolimus

Who may qualify

Ages: 1 year to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (6 listed)

Recipients of primary liver (cadaver/liver, whole/segmental) transplants 5- 30 years old.
Rejection-free post-transplant course for at least 3 months
Renal dysfunction (15% decrease in age-adjusted calculated creatinine clearance)
Hypertension requiring anti-hypertensive mediations.
Informed consent.

Key exclusion criteria (6 listed)

Rejection or infections within 3 months of enrollment.
Intent to continue TAC
Active participation in ongoing studies of immunosuppressive agents.
Lack of informed consent.
Pregnant or breast feeding

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SirolimusAlso: Sirolimus (Rapamycin), Tacrolimus (FK506)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's 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 GFR evaluation, or a few days later at the convenience of the subject.	Drug	Sirolimus

Primary outcome

Early and Late Pharmacokinetics of Sirolimus (SRL)
Time frame: 1 year
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.

3 secondary outcomes

PK Parameters for Tacrolimus and Sirolimus
Time frame: 12 months
SRL Can Substitute TAC
Time frame: 12 months
SRL Prevent TAC-related Side Effects
Time frame: 1 year

Results and safety

Results posted to the registry on 21 Apr 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sirolimus	3	3

Primary outcome: Early and Late Pharmacokinetics of Sirolimus (SRL)

Time frame: 1 year

Population analysed: 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.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 1 year. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sirolimus	0 of 3 (0%)	0 of 3 (0%)	Not reported

Limitations and caveats (from the sponsor): Complete follow-up failed, due to early study termination as a result of FDA black box warning (6/11/2009) about Sirolimus in liver transplant recipients (risk of thrombosis and death).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Hypertension

Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Enrolling by invitation
Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle
Pregnancy Related, Hypertension

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Rakesh Sindhi principal investigator

UPitt

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Sirolimus in people with Hypertension, run by University of Pittsburgh.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Early and Late Pharmacokinetics of Sirolimus (SRL) (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01709136.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2023.