Clinical trial NCT03968588: Standard- Versus Reduced-dose Tacrolimus Combined With Generic Mycophenolate Mofetil in De Novo Renal Transplantation
Official title: Comparative Clinical Study of Reduced Dose of Tacrolimus and Standard Dose of Mycophenolate Mofetil vs. Conventional Dose of Tacrolimus and Reduced Dose of Mycophenolate Mofetil in De Novo Renal Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Disorder Related to Renal Transplantation
Lead sponsor: Ajou University School of Medicine
Sponsor class: OTHER
First posted: 2019-05-30
Enrollment: 108
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A prospective, multicenter, open-label, randomized and parallel-group clinical trial was conducted at four transplant centers in Korea. This clinical study was designed to compare the efficacy and tolerability of reduced-dose tacrolimus with standard-dose mycophenolate mofetil (MMF) versus standard-dose tacrolimus with reduced-dose MMF.

Detailed description: A prospective, multicenter, open-label, randomized and parallel-group clinical trial was conducted at four transplant centers in Korea. The total sample size was 108 and eligible patients were randomly assigned in a 1:1 ratio to either study or control group. For six months study period, graft function, the incidence of efficacy failure and adverse events were compared.

The total sample size was 108 and eligible patients were randomly assigned in a 1:1 ratio to either study or control group: The study group (reduced-dose tacrolimus + standard-dose MMF) or the control group (standard-dose tacrolimus + reduced-dose MMF). Restricted block randomization was applied to this study and both the enrolled subjects and care providers were blinded until randomization was done. A difference in the mean estimated glomerular filtration rates (eGFR) of 16 mL/min/1.73m2 was considered a clinically meaningful margin of non-inferiority. A sample size of 108 for both groups was calculated for the primary endpoint by assuming a significance level of 0.025 with a power of at least 95% and adjusted for a potential dropout rate of 20%.

The primary efficacy endpoint was the renal graft function assessed with eGFR by MDRD formula at 6 months post-transplant. The secondary endpoints included (1) the incidence of treatment failure that included biopsy-confirmed acute rejection (BCAR), graft loss, death, or loss to follow-up until 6 months post-transplant; (2) recipients and grafts' survival rates; (3) 24-hour urine proteinuria and creatinine clearance at 6 months post-transplant. Recipients with clinical findings suggestive of acute rejection underwent biopsies before initiation or within 48 hours of anti-rejection therapy and biopsy specimens were graded according to Banff Classification criteria.

Safety endpoints included (1) all adverse event defined as any medical occurrence including worsening of a preexisting medical condition; (2) opportunistic infections; (3) malignancies; (4) abnormal laboratory findings; and (5) any abnormal physical findings or vital signs. Severe adverse events were defined as any adverse events with undesirable signs, symptoms, or medical conditions that met any one of the following criteria: 1) was fatal or life-threatening, 2) resulted in persistent or significant disability/incapacity, 3) required hospitalization or the prolongation of existing hospitalization, 4) was a congenital anomaly/birth defect, or 5) was an important medical event that might deteriorate the patient and require medical or surgical intervention to prevent one of the other outcomes listed above.18 All adverse events were coding using WHOART 2009 version.

Eligibility criteria: Inclusion Criteria:

* Recipients (aged 20-65) of a single (first or second) renal allograft from living or deceased donor.

Exclusion Criteria:

* comprised of recipients with multiple organ transplants
* double kidney transplant or organs donated after cardiac death
* recipients previously organ transplanted except kidney
* ABO-incompatible transplants
* recipients with antibodies against the human leukocyte antigens of the donor organ
* history of malignancy in the previous 5 years (except successfully treated localized non-melanoma skin cancer and thyroid cancer)
* leukocyte counts of less than 2,500 per μL, or neutrophils less than 1,500 per μL, or platelets less than 50,000 per μL
* evidence of active systemic infection requiring the use of antibiotics, human immunodeficiency virus infection, or chronic active hepatitis B or C

Primary outcomes:
measure: renal graft function
timeFrame: 6 months post-transplant
Secondary outcomes:
measure: incidence of treatment failure
timeFrame: 6 months post-transplant
measure: recipients and grafts' survival rates
timeFrame: 6 months post-transplant
measure: 24-hour urine proteinuria and creatinine clearance
timeFrame: 6 months post-transplant
Other outcomes:
Locations:
city: Jeonju
country: Korea, Republic of
facility: Chonbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
Study officials:
affiliation: Department of surgery, Ajou University School of Medicine
name: Chang-Kwon Oh, M.D
role: PRINCIPAL_INVESTIGATOR
References: