Heart TransplantationPhase 2NCT01655563
Pharmacogenetic Trial of Tacrolimus After Pediatric Transplantation
A Phase 2 study testing Tacrolimus in people with Heart Transplantation and Liver Transplantation, run by The Hospital for Sick Children at 1 site in Canada.
Trial summary
Tacrolimus is a standard and widely used maintenance immunosuppressive agent after solid organ transplantation.The purpose of this trial is to determine if dosing of tacrolimus through genetics will help in early attainment and maintenance of the correct dosage level in the early post-transplant period. Read more about this study
- Who is it for?
- Ages 1 day to 18 years
- Conditions the study is for
- Heart Transplantation, Liver Transplantation, Kidney Transplantation
- What is being tested?
- Tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2011to Feb 2016
- Phase
- Phase 2
- 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 day to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age < 18 years old
- Assessed and/or listed for heart, kidney, liver transplantation
- Planned oral or enteral maintenance immunosuppression with tacrolimus post transplant
- Informed consent of legal guardian
Who cannot join
- Contra-indications to oral or enteral tacrolimus
- Co-morbidities that preclude standard dosing e.g. significant renal or hepatic insufficiency
- Participation in other investigational drug trials within 30 days of study initiation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pharmacogenetic Trial of Tacrolimus Dosing After Pediatric Transplantation
Tacrolimus is a standard and widely used maintenance immunosuppressive agent after solid organ transplantation.The purpose of this trial is to determine if dosing of tacrolimus through genetics will help in early attainment and maintenance of the correct dosage level in the early post-transplant period. This pilot dose-finding trial will help to determine a dosing strategy guided by genotypes and age for solid organ transplant recipients that will be further validated through a multi-centre trial as an immediate next step. The study hypothesizes that dosage levels determined through age and genotype will be attained faster and more accurately than the standard dosing procedures in the 14-days after the transplant. Further, this study hypothesizes that a genotype and age dosing strategy will cause a faster recovery (tested through the kidneys' ability to clear creatine from the blood) and result in lower frequencies of adverse effects and rejection of the transplant.
- Being tested
- Tacrolimus
- Keywords
- Transplant, Pediatrics, Tacrolimus, Prograf
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TacrolimusDrug
Also called Prograf
Tacrolimus, a calcineurin inhibitor, is the commonest immunosuppressive agent used for maintenance immunosuppression after solid organ transplantation. The mechanism of action involves binding to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin and calcineurin is then formed and the phosphatase activity of calcineurin is inhibited. This prevents the generation of nuclear factor of activated T-cells, a nuclear component, resulting in inhibition of transcription of lymphokines (interleukin-2, γ-interferon). The net result is the inhibition of T-lymphocyte activation.Tacrolimus is metabolized primarily by the CYP3A enzymes in the liver particularly the CYP3A5.
| Study group | Role | What they receive |
|---|---|---|
| Standard Dosing Arm | Active comparator | Patients in the standard arm will receive standard starting dose of tacrolimus that is clinically used i.e. 0.1 mg/kg/dose twice a day. Receives: Drug: Tacrolimus |
| Pharmacogenetic Arm | Experimental | Patients in the pharmacogenetic arm will receive a starting dose that is assigned based on age and CYP3A5 expressor status. Patients that are CYP3A5 expressors will receive the higher end of the dose range compared to non-expressors. All doses recommended represent clinically acceptable and safe dose ranges used at our institution.
CYP3A5 non-expressor starting dose:
Greater than 6 years of age - 0.075 mg/kg/dose q12 hours; Less than or equal to 6 years of age - 0.1 mg/kg/dose q12 hours
CYP3A5 expressor starting dose:
Greater than 6 years of age - 0.15 mg/kg/dose q12 hours; Less than or equal to 6 years of age - 0.2 mg/kg/dose q12 hours Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Achieve Therapeutic Tacrolimus Drug Concentrations
The primary outcome (efficacy) was time to achieve therapeutic tacrolimus trough concentrations
Measured: From Baseline to 30 days post-dose
Time to Maintain Stable Therapeutic Trough Concentrations
Defined as two consecutive concentrations at least 48 hours apart in the therapeutic range without any changes in tacrolimus dose
Measured: From Baseline to 30 days post-dose
Secondary outcomes (1)
Clinical Adverse Events
The effect of pharmacogenetic dosing of tacrolimus for 48 hours on the frequency clinical adverse effects over 30±3 days.
Measured: Over 30 days, +/- 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2012 (estimated)
- Study startSep 2011
- Primary completionFeb 2016
- Study completionFeb 2016
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart TransplantationStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Seema Mital, The Hospital for Sick Children
- Investigators
- Seema Mital, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01655563
- Sponsor's protocol ID
- 1000026524
- Status last verified
- Nov 2019
- First submitted
- 27 Jul 2012
- Last updated
- 13 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Min S, Papaz T, Lafreniere-Roula M, Nalli N, Grasemann H, Schwartz SM, Kamath BM, Ng V, Parekh RS, Manlhiot C, Mital S. A randomized clinical trial of age and genotype-guided tacrolimus dosing after pediatric solid organ transplantation. Pediatr Transplant. 2018 Nov;22(7):e13285. doi: 10.1111/petr.13285. Epub 2018 Sep 3.
PubMed 30178515
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacogenetic Trial of Tacrolimus Dosing After Pediatric Transplantation
- ClinicalTrials.gov ID
- NCT01655563
- Acronym / sponsor ID
- 1000026524
- Keywords
- Transplant, Pediatrics, Tacrolimus, Prograf
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- Sep 2011
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 2 Aug 2012 (estimated)
- Results
- Posted 28 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Tacrolimus is a standard and widely used maintenance immunosuppressive agent after solid organ transplantation.The purpose of this trial is to determine if dosing of tacrolimus through genetics will help in early attainment and maintenance of the correct dosage level in the early post-transplant period. This pilot dose-finding trial will help to determine a dosing strategy guided by genotypes and age for solid organ transplant recipients that will be further validated through a multi-centre trial as an immediate next step. The study hypothesizes that dosage levels determined through age and genotype will be attained faster and more accurately than the standard dosing procedures in the 14-days after the transplant. Further, this study hypothesizes that a genotype and age dosing strategy will cause a faster recovery (tested through the kidneys' ability to clear creatine from the blood) and result in lower frequencies of adverse effects and rejection of the transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Dosing Arm | Active comparator | Drug: TacrolimusPatients in the standard arm will receive standard starting dose of tacrolimus that is clinically used i.e. 0.1 mg/kg/dose twice a day. |
| Pharmacogenetic Arm | Experimental | Drug: TacrolimusPatients in the pharmacogenetic arm will receive a starting dose that is assigned based on age and CYP3A5 expressor status. Patients that are CYP3A5 expressors will receive the higher end of the dose range compared to non-expressors. All doses recommended represent clinically acceptable and safe dose ranges used at our institution. CYP3A5 non-expressor starting dose: Greater than 6 years of age - 0.075 mg/kg/dose q12 hours; Less than or equal to 6 years of age - 0.1 mg/kg/dose q12 hours CYP3A5 expressor starting dose: Greater than 6 years of age - 0.15 mg/kg/dose q12 hours; Less than or equal to 6 years of age - 0.2 mg/kg/dose q12 hours |
Who may qualify
- Ages
- 1 day to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Age < 18 years old
- Assessed and/or listed for heart, kidney, liver transplantation
- Planned oral or enteral maintenance immunosuppression with tacrolimus post transplant
- Informed consent of legal guardian
Key exclusion criteria (3 listed)
- Contra-indications to oral or enteral tacrolimus
- Co-morbidities that preclude standard dosing e.g. significant renal or hepatic insufficiency
- Participation in other investigational drug trials within 30 days of study initiation
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 |
|---|---|---|
| TacrolimusAlso: PrografTacrolimus, a calcineurin inhibitor, is the commonest immunosuppressive agent used for maintenance immunosuppression after solid organ transplantation. The mechanism of action involves binding to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin and calcineurin is then formed and the phosphatase activity of calcineurin is inhibited. This prevents the generation of nuclear factor of activated T-cells, a nuclear component, resulting in inhibition of transcription of lymphokines (interleukin-2, γ-interferon). The net result is the inhibition of T-lymphocyte activation.Tacrolimus is metabolized primarily by the CYP3A enzymes in the liver particularly the CYP3A5. | Drug | Pharmacogenetic Arm, Standard Dosing Arm |
Primary outcome
Time to Achieve Therapeutic Tacrolimus Drug Concentrations
Time frame: From Baseline to 30 days post-dose
The primary outcome (efficacy) was time to achieve therapeutic tacrolimus trough concentrations
Time to Maintain Stable Therapeutic Trough Concentrations
Time frame: From Baseline to 30 days post-dose
Defined as two consecutive concentrations at least 48 hours apart in the therapeutic range without any changes in tacrolimus dose
1 secondary outcome
Clinical Adverse Events
Time frame: Over 30 days, +/- 3 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30178515Min S, Papaz T, Lafreniere-Roula M, Nalli N, Grasemann H, Schwartz SM, Kamath BM, Ng V, Parekh RS, Manlhiot C, Mital S. A randomized clinical trial of age and genotype-guided tacrolimus dosing after pediatric solid organ transplantation. Pediatr Transplant. 2018 Nov;22(7):e13285. doi: 10.1111/petr.13285. Epub 2018 Sep 3.
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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.
Seema Mital, MD principal investigator
The Hospital for Sick Children
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tacrolimus in people with Heart Transplantation and Liver Transplantation, run by The Hospital for Sick Children at 1 site in Canada.
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 4 inclusion and 3 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: finished, as of the sponsor's last update on 13 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
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 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.
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 28 Aug 2019). 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?
Time to Achieve Therapeutic Tacrolimus Drug Concentrations (time frame: From Baseline to 30 days post-dose). The study lists 2 primary outcomes in all. 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 NCT01655563, which also lists 1 linked publication.
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 13 Dec 2019.