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Kidney TransplantPhase 4NCT03644485

Clinical Outcome of Delayed or Standard Prograf Together With Induction Therapy Followed by Conversion to Advagraf in Donation After Cardiac (or Circulatory) Death (DCD) Kidney Transplant Recipients

A Phase 4 study testing Tacrolimus immediate-release formulation, Tacrolimus prolonged-release formulation and Induction therapy in people with Kidney Transplant, run by Astellas Pharma China, Inc. at 14 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to confirm non-inferiority of delayed Prograf treatment to standard Prograf treatment in the incidence of delayed graft function (DGF) within 1 week between the 2 immunosuppressive (IS) treatment groups: delayed or standard Prograf together with induction therapy, and then convert to… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Kidney Transplant
What is being tested?
Tacrolimus immediate-release formulation, Tacrolimus prolonged-release formulation and Induction therapy
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
284 participants
Where
14 sitesChina
Study dates
21 Oct 2018to 15 Jul 2022
Phase
Phase 4
Are there results?
None posted in the registry

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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject has end-stage kidney disease who is a suitable candidate for primary DCD kidney transplantation.
  • Subject is a resident of China.
  • Subject is scheduled to undergo DCD renal allograft transplantation with compatible ABO blood type.
  • Subject has peak panel-reactive antibodies (PRA) < 10% or "Negative" test result.
  • Subject must be a recipient of a DCD kidney and receive the organ distributed by China Organ Transplant Response System only.
  • Female subject must either:
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  • Be of non-childbearing potential: Postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or documented surgically sterile
  • Or, if of childbearing potential: Agree not to try to become pregnant throughout the study period and have a negative blood pregnancy test at screening.
  • A sexually active male or female subject is utilizing highly effective forms of birth control starting at screening and throughout the study period if the risk of conception exists.
  • Subject agrees not to participate in another interventional study while participating in the present study from 1 month before randomization to 1 month after the last dose of investigational drug.

Who cannot join

  • Subject has previously received or is receiving an organ transplant other than kidney.
  • Subject is receiving double-kidney transplant.
  • Recipients of Maastricht Class I, II, and V donor organs.
  • Recipients of Maastricht Class III and IV donor organs without a full complement of intensive care unit and intraoperative records.
  • Subject has cold ischemia time of allograft > 24 hours before kidney transplantation surgery.
  • Subject has known contraindication to administration of tacrolimus (Prograf or Advagraf), or other macrolides.
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  • Subject is unlikely to comply with the visits scheduled in the protocol or has a history of non-compliance.
  • Subject has evidence of active liver disease or the presence of a chronic active hepatitis B or C within 1 month prior to kidney transplant surgery.
  • Recipient or donor is seropositive for human immunodeficiency virus.
  • Subject has active systemic infection requiring the use of antimicrobial agents within 1 week prior to kidney transplant surgery.
  • Subject has current malignancy or a history of malignancy (within the past 5 years), except non- metastatic basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix that has been treated successfully.
  • Subject has medical or psychological conditions which would preclude compliance with the study requirements.
  • Subject has any condition, including any uncontrolled disease state other than end-stage kidney disease, that constitutes an inappropriate risk or a contraindication for participation in the study, or that could interfere with the study objectives, conduction, or evaluation.
  • Female subject who breastfeed or donate ova starting at screening and throughout the study period.
  • Male subject who donate sperm starting at screening and throughout the study period.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

China14 sites
  • Site CN08608

    Beijing

  • Site CN08619

    Beijing

  • Site CN08609

    Changsha

  • Site CN08604

    Guangzhou

  • Site CN08614

    Hangzhou

  • Site CN08617

    Hangzhou

  • Site CN08610

    Nanjing

  • Site CN08618

    Nanjing

  • Site CN08612

    Shanghai

  • Site CN08603

    Tianjin

  • Site CN08621

    Wenzhou

  • Site CN08602

    Wuhan

  • Site CN08613

    Wuhan

  • Site CN08605

    Xi'an

Other trials in China

About this study

Official title: Clinical Outcome of Delayed or Standard Prograf Together With Induction Therapy Followed by Conversion to Advagraf in Donation After Cardiac (or Circulatory) Death (DCD) Kidney Transplant Recipients: A Randomized, Open-label, Multicenter Clinical Trial

The purpose of this study is to confirm non-inferiority of delayed Prograf treatment to standard Prograf treatment in the incidence of delayed graft function (DGF) within 1 week between the 2 immunosuppressive (IS) treatment groups: delayed or standard Prograf together with induction therapy, and then convert to Advagraf usage in donation after cardiac (or circulatory) death (DCD) kidney transplant recipients.

This study will also compare the clinical outcome within 6 month post-transplant between the 2 IS treatment groups and compare the safety throughout study period between the 2 IS treatment groups.

Being tested
Tacrolimus immediate-release formulation, Tacrolimus prolonged-release formulation, Induction therapy, Mycophenolic acid drugs, Corticosteroids
Keywords
kidney transplant, Tacrolimus, Prograf, Advagraf, FK506

What participants receive

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

  • Tacrolimus immediate-release formulationDrug

    Also called Prograf, FK506

    oral

  • Tacrolimus prolonged-release formulationDrug

    Also called Advagraf, FK506

    oral

  • Induction therapyDrug

    All participants will receive induction therapy. The dosage and administration of induction immunotherapy will be a single kind of drug determined by the investigator.

  • Mycophenolic acid drugsDrug

    All participants will receive mycophenolic acid drugs in combination with corticosteroids. The dosage and administration of mycophenolic acid will be determined by the investigator.

  • CorticosteroidsDrug

    All participants will receive corticosteroids in combination with mycophenolic acid drugs. The dosage and administration of corticosteroids will be determined by the investigator.

Study groups in NCT03644485
Study groupRoleWhat they receive
Standard Prograf groupExperimentalParticipants received from day 1 tacrolimus immediate-release formulation (Prograf) 0.1 - 0.15 milligrams/kilograms/day (mg/kg/day) orally at 12-hour interval (twice daily 1 hour before meal or 2 hours after meal) for approximately 1 month. At 1 month after Kidney transplant, Prograf was converted to Advagraf on a 1:1 (mg: mg) total daily dose basis. The Advagraf was administered orally once daily in the morning, 1 hour before the breakfast; the whole blood target trough level for Advagraf was maintained as 6 - 12 nanograms/milliliter(ng/mL) within months 2 to 3, and 6 - 8 ng/mL within months 4 to 6.
Receives: Drug: Tacrolimus immediate-release formulation; Drug: Tacrolimus prolonged-release formulation; Drug: Induction therapy; Drug: Mycophenolic acid drugs; Drug: Corticosteroids
Delayed Prograf groupExperimentalParticipants received from day 3 to 5 Prograf 0.1 - 0.15 mg/kg/day orally at 12-hour interval (twice daily 1 hour before meal or 2 hours after meal) for approximately 1 month. At 1 month after Kidney transplant, Prograf was converted to Advagraf on a 1:1 (mg: mg) total daily dose basis. The Advagraf was administered orally once daily in the morning, 1 hour before the breakfast; the whole blood target trough level for Advagraf was maintained as 6 - 12 ng/mL within months 2 to 3, and 6 - 8 ng/mL within months 4 to 6.
Receives: Drug: Tacrolimus immediate-release formulation; Drug: Tacrolimus prolonged-release formulation; Drug: Induction therapy; Drug: Mycophenolic acid drugs; Drug: Corticosteroids

What is being measured

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

  1. Incidence of delayed graft function (DGF)

    DGF is defined as dialysis requirement during the first post-transplant week (7 days).

    Measured: Up to Day 7 after transplantation

Secondary outcomes (11)
  1. Incidence of acute rejection (AR)

    The reporting of AR includes any biopsy-proven or clinically-suspected rejection of a subject after transplantation.

    Measured: Up to Month 6 after transplantation

  2. Renal function assessed by estimated glomerular filtration rate (eGFR)

    eGFR will be derived using the abbreviated Modification of Diet in Renal Disease (MDRD) formula.

    Measured: Up to Month 6 after transplantation

  3. Renal function assessed by serum creatinine

    Serum creatinine will be measured from serum sample collected.

    Measured: Up to Month 6 after transplantation

  4. Renal function assessed by urea nitrogen

    Urea nitrogen will be measured from serum sample collected.

    Measured: Up to Month 6 after transplantation

  5. Subject survival

    Subject survival is the time from the date of transplantation to the date of death or the date of the last follow-up. Subject survival will be estimated using Kaplan Meier estimates and compared by log rank test.

    Measured: Up to Month 6 after transplantation

  6. Graft survival

    Graft survival is an estimate of the probability of the transplant functioning at a finite time after transplantation. Graft survival will be calculated from the date of transplantation to the date of irreversible graft failure or the date of the last follow-up during the period when the transplant is still functioning or to the date of death.

    Measured: Up to Month 6 after transplantation

  7. Safety assessed by incidence of treatment-emergent adverse events (TEAEs)

    Adverse events (AEs) will be coded using the latest version of MedDRA. TEAE is defined as any AE following the transplantation until the end of the study.

    Measured: Up to Month 7 after transplantation

  8. Safety assessed by incidence of serious adverse events (SAEs)

    AE is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event.

    Measured: Up to Month 7 after transplantation

  9. Number of participants with laboratory test abnormalities and/or AEs

    Number of participants with potentially clinically significant laboratory values.

    Measured: Up to Month 7 after transplantation

  10. Number of participants with vital sign abnormalities and/or AEs

    Number of participants with potentially clinically significant vital sign values.

    Measured: Up to Month 7 after transplantation

  11. Number of participants with 12-lead electrocardiograms (ECG) abnormalities and/or AEs

    ECG will be performed in the supine position after the subject has been breathing quietly for 5 minutes. Any clinically significant adverse changes on the ECG will be reported as AEs.

    Measured: Up to Month 7 after transplantation

Timeline

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

  1. First posted23 Aug 2018
  2. Study start21 Oct 2018
  3. Primary completion15 Jul 2022
  4. Study completion15 Jul 2022

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
284 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03644485
Sponsor's protocol ID
506-MA-3186
Status last verified
Oct 2024
First submitted
22 Aug 2018
Last updated
31 Oct 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Publications

  • Oliveras L, Lopez-Vargas P, Melilli E, Codina S, Royuela A, Coloma Lopez A, Fava A, Manonelles A, Couceiro C, Lloberas N, Cruzado JM, Montero N. Delayed initiation or reduced initial dose of calcineurin-inhibitors for kidney transplant recipients at high risk of delayed graft function. Cochrane Database Syst Rev. 2025 Apr 8;4(4):CD014855. doi: 10.1002/14651858.CD014855.pub2.

    PubMed 40197799

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Tacrolimus immediate-release formulation, Tacrolimus prolonged-release formulation and Induction therapy in people with Kidney Transplant, run by Astellas Pharma China, Inc. at 14 sites in China.

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 10 inclusion and 15 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 31 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in China. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of delayed graft function (DGF) (time frame: Up to Day 7 after transplantation). 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 NCT03644485, 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 31 Oct 2024.

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