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

NCT ID: NCT03644485

Last Updated: 2024-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 284 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-21
• Study Completion Date: 2022-07-15

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.

Conditions

Kidney Transplant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard Prograf group

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.

Group Type: EXPERIMENTAL

Tacrolimus immediate-release formulation

Intervention Type: DRUG

oral

Tacrolimus prolonged-release formulation

Intervention Type: DRUG

oral

Induction therapy

Intervention Type: DRUG

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 drugs

Intervention Type: DRUG

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

Corticosteroids

Intervention Type: DRUG

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 group

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.

Group Type: EXPERIMENTAL

Tacrolimus immediate-release formulation

Intervention Type: DRUG

oral

Tacrolimus prolonged-release formulation

Intervention Type: DRUG

oral

Induction therapy

Intervention Type: DRUG

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 drugs

Intervention Type: DRUG

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

Corticosteroids

Intervention Type: DRUG

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

Interventions

Tacrolimus immediate-release formulation

oral

Intervention Type: DRUG

Tacrolimus prolonged-release formulation

oral

Intervention Type: DRUG

Induction therapy

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

Intervention Type: DRUG

Mycophenolic acid drugs

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

Intervention Type: DRUG

Corticosteroids

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

Intervention Type: DRUG

Other Intervention Names

Prograf; FK506; Advagraf; FK506

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma China, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma China, Inc.

Locations

Site CN08608

Beijing, , China

Site CN08619

Beijing, , China

Site CN08609

Changsha, , China

Site CN08604

Guangzhou, , China

Site CN08614

Hangzhou, , China

Site CN08617

Hangzhou, , China

Site CN08610

Nanjing, , China

Site CN08618

Nanjing, , China

Site CN08612

Shanghai, , China

Site CN08603

Tianjin, , China

Site CN08621

Wenzhou, , China

Site CN08602

Wuhan, , China

Site CN08613

Wuhan, , China

Site CN08605

Xi'an, , China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 40197799 (View on PubMed)

Related Links

http://www.trialsummaries.com/Study/StudyDetails?id=14639&tenant=MT_AST_9011

Link to plain language summary of the study on the Trial Results Summaries website.

http://www.clinicaltrials.astellas.com/study/506-MA-3186/

Link to results and other applicable study documents on the Astellas Clinical Trials website.

Other Identifiers

506-MA-3186

Identifier Type: -

Identifier Source: org_study_id