AzTrials
AzTrials

Organ Transplant Failure or RejectionPhase 2CINERGYNCT05148715

Calcineurin Inhibitor in NEuRoloGically Deceased Donors to Decrease Kidney delaYed Graft Function (CINERGY)

A Phase 2 study testing Tacrolimus in people with Organ Transplant Failure or Rejection and Brain Death, run by Université de Sherbrooke at 9 sites in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The investigators hypothesize that preconditioning neurologically deceased organ donors with the calcineurin inhibitor tacrolimus will improve short and long-term transplant survival without causing harm. Read more about this study

Who is it for?
Ages 18 to 100 years
What is being tested?
Tacrolimus
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
414 participants
Where
9 sitesCanada
Study dates
11 Jul 2022to Jan 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Neurologically deceased donors who meet the inclusion and exclusion criteria will be eligible for participating in this study along with the correlating organ recipients who meet inclusion criteria.

Donor Inclusion Criteria:

  • ≥18 years of age;
  • Neurologically deceased;
  • Consent for deceased organ donation;
  • All organ recipients have been identified;
  • ≥ 1 kidney allocated to a recipient.

Donor Exclusion Criteria:

  • Known hypersensitivity to tacrolimus or polyoxyl 60 hydrogenated castor oil;
  • One or more organs allocated to a non-participating transplant program;
  • Unlikely access to study drug (e.g., due to supply issues, or pharmacist availability);
  • One or more organ recipients has not agreed to receive an organ from a donor participating in the study;
  • One or more organs are allocated to a recipient under the age of 18;
  • A transplant physician has judged that donor tacrolimus will be unsuitable for an intended recipient.

Recipient Inclusion Criteria

  • Organ/Transplant graft originated from a donor enrolled in this study.

No exclusion criteria.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Canada9 sites

  • L'Institut de Cardiologie de Montréal

    Montreal, Quebec, H1T 1C8

  • Hôpital Maisonneuve-Rosemont

    Montreal, Quebec, H1T 2M4

  • Centre Hospitalier Universitaire de Montréal

    Montreal, Quebec, H2X 3E4

  • Centre universitaire de santé McGill (CUSM)

    Montreal, Quebec, H4A 3J1

  • Centre Hospitalier Universitaire de Québec- Université Laval

    Québec, Quebec, G1V 4G2

  • Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ)

    Québec, Quebec, G1V 4G5

  • Centre de recherche CHUS

    Sherbrooke, Quebec, J1H 5N4

  • Vancouver General Hospital

    Vancouver, British Columbia, V5Z 1M9

  • St. Paul's Hospital

    Vancouver, British Columbia, V6Z 1Y6

Other trials in Canada

About this study

Official title: Calcineurin Inhibitor in NEuRoloGically Deceased Donors to Decrease Kidney delaYed Graft Function (CINERGY)-Pilot Trial

The investigators hypothesize that preconditioning neurologically deceased organ donors with the calcineurin inhibitor tacrolimus will improve short and long-term transplant survival without causing harm. Organ donors will be randomized to receive either 0.02 mg/kg ideal body weight (IBW) of tacrolimus single infusion or placebo before organ recovery. All corresponding recipients are enrolled and data is collected up to 7 days post-transplant to determine graft function and at 1 year to collect outcomes of vital status, re-transplantation and dialysis. The CINERGY Pilot Trial assesses feasibility for the main trial.

Read the detailed description

Background: Organ donation saves lives, and improves quality of life for thousands of people. But organ donation falls short of expectations for some patients who suffer early graft loss. During organ donation surgery, the supply of blood with oxygen and nutrients is suspended. When restored during transplant surgery, a cascade of inflammation perturbs the newly transplanted organ -causing ischemia-reperfusion injury. When severe, it can hinder transplant function in the early post-operative period, lead to profound critical illness, increase the risks of transplant rejection and chronic disease, and reduce the transplant lifespan. Administration of tacrolimus, a calcineurin inhibitor, to neurologically deceased donors may reduce ischemia-reperfusion injury in transplant recipients.

Objectives: The CINERGY Pilot Trial will test the feasibility of comparing tacrolimus to placebo for the prevention of delayed graft function in kidney recipients and establish the foundation for a large, multi-centre randomized controlled trial (RCT).

Methods: 90 neurologically deceased kidney donors will be randomized to either tacrolimus (0.02 mg/kg) or the corresponding placebo 4-8 hours before organ recovery. To be included in the CINERGY Pilot RCT, donors will need to meet inclusion criteria. All corresponding recipients are enrolled and their data is collected in the first 7 days and at 12 months after transplantation.

Outcomes: Feasibility: Donor accrual rate and consent rate of organ recipients. Safety: acute kidney injury, hyperkalemia and anaphylaxis in donors and recipients. Clinical: graft function within 7 days in all recipients, vital status, re-transplantation and need for dialysis at 12 months.

Relevance: This pilot study will inform the feasibility and design of a larger trial. Moreover, the CINERGY Pilot RCT will pave the way for future trials linking organ donation and transplantation across Canada.

Being tested
Tacrolimus, Placebo
Keywords
organ donation and transplantation
Medical subject headings
Rejection, Psychology, Brain Death

What participants receive

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

  • TacrolimusDrug

    Also called Prograf

    Single dose intravenous tacrolimus over 4 hour infusion at a dose of 0.02 mg/kg ideal body weight diluted with 0.9% sodium chloride starting 4-8 hours before scheduled organ recovery.

  • PlaceboDrug

    Single dose of intravenous 0.9% sodium chloride over 4 hour infusion, starting 4-8 hours before scheduled organ recovery.

Study groups in NCT05148715
Study groupRoleWhat they receive
TacrolimusExperimentalTacrolimus 0.02 mg/kg ideal body weight 4-8 hours before organ recovery
Receives: Drug: Tacrolimus
PlaceboPlacebo comparator0.9% sodium chloride 4-8 hours before organ recovery
Receives: Drug: Placebo

What is being measured

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

  1. Organ donor accrual rates

    One primary objective of this pilot study is to determine if a national multi-centre placebo randomized controlled trial (RCT) will be feasible with respect to: organ donor accrual.

    Measured: 6 to 12 months after the beginning of the trial

  2. Recipient consent rate

    Another primary objective of this pilot study is to determine if a national multi-centre placebo controlled RCT will be feasible with respect to the consent rates of organ recipients. Recipient consent rates will be assessed during analysis, analyzing the rate and reasons for non-enrolment.

    Measured: 6 to 12 months after the beginning of the trial

Secondary outcomes (19)

  1. Correlation between two methods for obtaining survival status

    We will compare 2 methods (Hospital records, Canadian Institute for Health Information) for obtaining recipient survival at 12 months post-transplant.

    Measured: 12 months post transplant

  2. Unexpected adverse events

    In donors and recipients, unexpected adverse events as identified by clinical staff will be reported and analyzed.

    Measured: Within 7 days post transplant

  3. Percentage of donors with acute kidney injury (AKI)

    AKI defined as defined as Kidney disease: Improving global outcome (KDIGO) stage II (or more): serum creatinine ≥ 2.0 times baseline OR a urine output <0.5mL/kg/h for ≥12 hours

    Measured: Within 4 hours after the end of the study drug infusion

  4. Percentage of donors with hyperkalemia

    Hyperkalemia defined as a potassium level > 5 mmol/L

    Measured: Within 4 hours after the end of the study drug infusion

  5. Percentage of donors hypertension during tacrolimus infusion

    Hypertension (systolic blood pressure ≥ 160 mmHg or mean arterial pressure ≥ 90 mmHg for > 15 minutes)

    Measured: Within 4 hours after the initiation of study drug infusion

  6. Percentage of donors with cardiac arrhythmia associated with tacrolimus infusion

    Cardiac arrhythmias defined as new onset of atrial fibrillation or flutter, ventricular tachycardia or fibrillation

    Measured: Within 4 hours after the initiation of study drug infusion

  7. Percentage of donors with anaphylaxis

    Anaphylaxis defined as per The American Academy of Allergy, Asthma and Immunology

    Measured: Within 4 hours after the initiation of study drug infusion

  8. Percentage of recipients with acute kidney injury

    AKI defined as defined as KDIGO stage II or more: serum creatinine ≥ 2.0 times baseline OR a urine output <0.5mL/kg/h for ≥12 hours

    Measured: Within 7 days post transplant

  9. Percentage of recipients with hyperkalemia

    Hyperkalemia defined as a potassium level > 5 mmol/L

    Measured: Within 7 days post transplant

  10. Percentage of recipients with anaphylaxis

    Anaphylaxis defined as per The American Academy of Allergy, Asthma and Immunology

    Measured: Within 7 days post transplant

  11. Recipient serum tacrolimus levels

    Clinical research staff will abstract routine serum tacrolimus levels (when measured) from hospital records over the first 7 days, along with local thresholds for toxic level.

    Measured: Within 7 days post transplant

  12. Percentage of liver recipients with early graft function

    At least ≥ 1 of the following criteria: Bilirubin ≥ 10 mg/dL , International normalized ratio (INR) ≥ 1.6 AST or ALT level > 2000 IU/

    Measured: Within 7 days post transplant

  13. Graft survival

    Need to be re-transplanted or to be on the re-transplant list.

    Measured: 12 months post transplant

  14. Recipient survival

    Recipient death

    Measured: 12 months post transplant

  15. Recipients requiring dialysis

    Recipient requirement for dialysis at 12 months

    Measured: 12 months post transplant

  16. Percentage of lungs recipients with severe primary graft dysfunction

    PaO2/FiO2 ratio <200 and diffuse infiltration/pulmonary edema on chest radiograph

    Measured: Within 3 days post transplant

  17. Percentage of kidney recipients with delayed graft function

    Requirement of ≥ 1 hemodialysis session

    Measured: Within 7 days post transplant

  18. Percentage of heart recipients with severe primary graft dysfunction

    Dependence on mechanical support

    Measured: Within 1 days post transplant

  19. Percentage of pancreas recipients with delayed graft function

    Requirement of ≥1 exogenous insulin at hospital discharge

    Measured: At hospital discharge, an average of 7 days

Timeline

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

  1. First posted8 Dec 2021
  2. Study start11 Jul 2022
  3. Primary completionDec 2025 (estimated)
  4. Study completionJan 2026 (estimated)

Resources

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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
414 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05148715
Sponsor's protocol ID
MP-31-2020-3348
Acronym
CINERGY
Status last verified
Apr 2025
First submitted
18 Oct 2021
Last updated
17 Apr 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • D'Aragon F, Selzner M, Breau R, Masse MH, Lamontagne F, Masse M, Chasse M, Carrier FM, Cardinal H, Chaudhury P, Weiss M, Lauzier F, Turgeon AF, Frenette AJ, Bolduc B, Ducharme A, Lamarche C, Couture E, Holdsworth S, Bertholz L, Talbot H, Slessarev M, Luke P, Boyd JG, Shamseddin MK, Burns KEA, Zaltzman J, English S, Knoll G, Dhanani S, Healey A, Hanna S, Rochwerg B, Oczkowski SJW, Treleaven D, Meade M; Canadian Critical Care Trials Group and the Canadian Donation and Transplant Research Program. Calcineurin Inhibitor in NEuRoloGically deceased donors to decrease kidney delayed graft function study: study protocol of the CINERGY Pilot randomised controlled trial. BMJ Open. 2024 Jun 13;14(6):e086777. doi: 10.1136/bmjopen-2024-086777.

    PubMed 38871657

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tacrolimus in people with Organ Transplant Failure or Rejection and Brain Death, run by Université de Sherbrooke at 9 sites in Canada.

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

Who may be eligible to take part?

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: under way, not looking for participants, as of the sponsor's last update on 17 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites 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. Some participants in this study may receive a placebo. 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?

This study is still under way. Results are not available in the source record yet.

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?

Organ donor accrual rates (time frame: 6 to 12 months after the beginning of the trial). 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 NCT05148715, 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 17 Apr 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in