Clinical trial NCT03644485: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Transplant
Keywords: kidney transplant
Tacrolimus
Prograf
Advagraf
FK506
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2018-08-23
Enrollment: 284
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Incidence of delayed graft function (DGF)
timeFrame: Up to Day 7 after transplantation
Secondary outcomes:
measure: Incidence of acute rejection (AR)
timeFrame: Up to Month 6 after transplantation
measure: Renal function assessed by estimated glomerular filtration rate (eGFR)
timeFrame: Up to Month 6 after transplantation
measure: Renal function assessed by serum creatinine
timeFrame: Up to Month 6 after transplantation
measure: Renal function assessed by urea nitrogen
timeFrame: Up to Month 6 after transplantation
measure: Subject survival
timeFrame: Up to Month 6 after transplantation
measure: Graft survival
timeFrame: Up to Month 6 after transplantation
measure: Safety assessed by incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to Month 7 after transplantation
measure: Safety assessed by incidence of serious adverse events (SAEs)
timeFrame: Up to Month 7 after transplantation
measure: Number of participants with laboratory test abnormalities and/or AEs
timeFrame: Up to Month 7 after transplantation
measure: Number of participants with vital sign abnormalities and/or AEs
timeFrame: Up to Month 7 after transplantation
measure: Number of participants with 12-lead electrocardiograms (ECG) abnormalities and/or AEs
timeFrame: Up to Month 7 after transplantation
Other outcomes:
Locations:
city: Beijing
country: China
facility: Site CN08608
city: Beijing
country: China
facility: Site CN08619
city: Changsha
country: China
facility: Site CN08609
city: Guangzhou
country: China
facility: Site CN08604
city: Hangzhou
country: China
facility: Site CN08614
city: Hangzhou
country: China
facility: Site CN08617
city: Nanjing
country: China
facility: Site CN08610
city: Nanjing
country: China
facility: Site CN08618
city: Shanghai
country: China
facility: Site CN08612
city: Tianjin
country: China
facility: Site CN08603
city: Wenzhou
country: China
facility: Site CN08621
city: Wuhan
country: China
facility: Site CN08602
city: Wuhan
country: China
facility: Site CN08613
city: Xi'an
country: China
facility: Site CN08605
Study officials:
affiliation: Astellas Pharma China, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: