NCT03644485

Brief 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 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
284

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Oct 2018

Longer than P75 for phase_4

Geographic Reach
1 country

14 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 22, 2018

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 23, 2018

Completed
2 months until next milestone

Study Start

First participant enrolled

October 21, 2018

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 15, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 15, 2022

Completed
Last Updated

October 31, 2024

Status Verified

October 1, 2024

Enrollment Period

3.7 years

First QC Date

August 22, 2018

Last Update Submit

October 29, 2024

Conditions

Keywords

kidney transplantTacrolimusPrografAdvagrafFK506

Outcome Measures

Primary Outcomes (1)

  • Incidence of delayed graft function (DGF)

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

    Up to Day 7 after transplantation

Secondary Outcomes (11)

  • Incidence of acute rejection (AR)

    Up to Month 6 after transplantation

  • Renal function assessed by estimated glomerular filtration rate (eGFR)

    Up to Month 6 after transplantation

  • Renal function assessed by serum creatinine

    Up to Month 6 after transplantation

  • Renal function assessed by urea nitrogen

    Up to Month 6 after transplantation

  • Subject survival

    Up to Month 6 after transplantation

  • +6 more secondary outcomes

Study Arms (2)

Standard Prograf group

EXPERIMENTAL

Participants 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.

Drug: Tacrolimus immediate-release formulationDrug: Tacrolimus prolonged-release formulationDrug: Induction therapyDrug: Mycophenolic acid drugsDrug: Corticosteroids

Delayed Prograf group

EXPERIMENTAL

Participants 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.

Drug: Tacrolimus immediate-release formulationDrug: Tacrolimus prolonged-release formulationDrug: Induction therapyDrug: Mycophenolic acid drugsDrug: Corticosteroids

Interventions

oral

Also known as: Prograf, FK506
Delayed Prograf groupStandard Prograf group

oral

Also known as: Advagraf, FK506
Delayed Prograf groupStandard Prograf group

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

Delayed Prograf groupStandard Prograf group

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

Delayed Prograf groupStandard Prograf group

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

Delayed Prograf groupStandard Prograf group

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • 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.

You may not qualify if:

  • 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.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

Site CN08608

Beijing, China

Location

Site CN08619

Beijing, China

Location

Site CN08609

Changsha, China

Location

Site CN08604

Guangzhou, China

Location

Site CN08614

Hangzhou, China

Location

Site CN08617

Hangzhou, China

Location

Site CN08610

Nanjing, China

Location

Site CN08618

Nanjing, China

Location

Site CN08612

Shanghai, China

Location

Site CN08603

Tianjin, China

Location

Site CN08621

Wenzhou, China

Location

Site CN08602

Wuhan, China

Location

Site CN08613

Wuhan, China

Location

Site CN08605

Xi'an, China

Location

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Interventions

TacrolimusNeoadjuvant TherapyAdrenal Cortex Hormones

Intervention Hierarchy (Ancestors)

MacrolidesLactonesOrganic ChemicalsCombined Modality TherapyTherapeuticsHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

  • Medical Director

    Astellas Pharma China, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 22, 2018

First Posted

August 23, 2018

Study Start

October 21, 2018

Primary Completion

July 15, 2022

Study Completion

July 15, 2022

Last Updated

October 31, 2024

Record last verified: 2024-10

Data Sharing

IPD Sharing
Will not share

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/.

Locations