Condition category
Urological and Genital Diseases
Date applied
15/08/2016
Date assigned
15/06/2017
Last edited
24/05/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
A kidney transplant is the transfer of a healthy kidney from one person into the body of a person who has little or no kidney function. People who receive a kidney transplant usually need to take immunosuppressant medications for the rest of their life to prevent the body's immune system from attacking the new kidney (graft loss). For over 20 years calcineurin inhibitor (CNI) drugs such as tacrolimus have been used for immunosuppression. There are many different causes of graft loss including some risk factors that could be managed through improvement of the immunosuppressive treatment. Approaches taken to improve treatment include adding other immunosuppressive treatments to CNIs, especially those with complementary ways of working and different side effects. Tacrolimus in combination with mycophenolic acid (MPA) is an effective immunosuppressive treatment for kidney transplant recipients. The combination of tacrolimus and sirolimus has also been shown to provide effective immunosuppression. The strong combined immunosuppressive effect of tacrolimus plus sirolimus allows the dose of tacrolimus to be reduced when used in combination with sirolimus. The aim of this study is to compare the use of sirolimus plus tacrolimus with tacrolimus plus mycofenolic acid in kidney transplantation.

Who can participate?
Patients aged 18-65 receiving their first kidney transplant

What does the study involve?
Patients are randomly allocated into two groups. After receiving their kidney transplant one group is treated with sirolimus plus tacrolimus and the other group is treated with tacrolimus plus mycofenolic acid. Both groups are followed up over 1 year after their transplant to assess their kidney function.

What are the possible benefits and risks of participating?
The new treatment may reduce the incidence of viral infections and cancer. As with all immunosuppressive treatments there is a risk of transplant rejection and infections.

Where is the study run from?
Labbafinejad Hospital (Iran)

When is the study starting and how long is it expected to run for?
September 2016 to September 2017

Who is funding the study?
Sanofi

Who is the main contact?
Dr Behrang Alipour Abedi

Trial website

Contact information

Type

Scientific

Primary contact

Dr Behrang Alipour Abedi

ORCID ID

Contact details

9th Boostan
Pasdaran St
Tehran
5546859685
Iran

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Comparison of de novo sirolimus plus tacrolimus with tacrolimus plus mycofenolic acid in renal transplantation: a randomized clinical trial

Acronym

Study hypothesis

Sirolimus plus tacrolimus has the same effect as tacrolimus plus mycofenolic acid in renal transplantation outcomes.

Ethics approval

Shahid Beheshti University of Medical Sciences, 15/08/2016, ref: IR.SBMU.UNRC.1394.25

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Kidney transplantation

Intervention

Participants are randomised by block randomisation to group A or B:

Group A:
Thymoglobulin 3mg/kg divided in 3-4 days
Myfortic (mycophenolic acid) 360 mg x 3 for 7 days then 720 mg/d (initial dose should be started from 1 day before TX)
Prograf (tacrolimus) 0.1 mg/kg/d trough level to reach 8-10 ng for 90 d then 5-8 thereafter (initial dose should be started from 1 day before TX)
Prednisolone MP250 x 2 d then 1mg /kg (max 60 mg) x 3 d, taper 5 mg/d, 15 mg at day 14, 10 mg day 30, 5 mg day 60 and thereafter
Ganciclovir during first 8 days
After using ganciclovir Valcyte (valganciclovir hydrochloride) should be used for 90 days

Group B:
Thymoglobulin 3mg/kg divided in 3-4 days
Prograf (tacrolimus) 0.08 mg/kg to reach trough 6-7 ng/ml for 6 m then toward 4-5 after 6 m (initial dose should be started from 1 day before TX)
Rapamune (sirolimus) 2 mg first d within 96 h of surgery then 1 mg/d reaching trough level around 3-5 for first 6 mo then trough 6-8 ng/ml thereafter (sum of sirolimus + tac around 10-12)
Prednisolone MP250 x 2d then 1 mg /kg (max 60 mg) x 3 d, taper 5 mg/d, 15 mg at day 14, 10 mg day 30, 5 mg day 60 and thereafter
Ganciclovir IV during first 8 days
After using ganciclovir Valcyte (valganciclovir hydrochloride) should be used for 90 days

Participants are followed up at 1-14 days, 1 month, 6 weeks, 2 months, 10 weeks, 3 months, 4 months, 5 months, 6 months, 8 months, 10 months and 12 months.

Intervention type

Drug

Phase

Not Applicable

Drug names

Thymoglobulin, mycophenolic acid, tacrolimus, prednisolone, ganciclovir, valganciclovir, sirolimus

Primary outcome measures

1. Estimation of glomerular filtration rate (GFR) based on Modification of Diet in Renal Disease (MDRD) at months 3, 6 and 12
2. Biopsy proven acute rejection (BPAR) (indication for biopsy when creatinine rise > 0.3 mg/dl for continuous 2 days) at months 3 and 12

Secondary outcome measures

1. Incidence of borderline changes, subclinical acute cellular rejection and subclinical antibody mediated rejection (ABMR), measured by protocol biopsy at month 4
2. Incidence of new-onset diabetes after transplantation (NODAT) at 3, 6, 12 months
3. Incidence of donor specific anti-HLA antibodies (DSA), measured using solid phase ELISA at 4 and 12 months
4. Incidence of hypertension at 3, 6 and 12 months
5. Incidence of hyperlipidemia (total cholesterol, LDL-C, HDL-C and TG) at months 3, 6 and 12
6. Incidence of CMV viremia ( >2000 copies/ml) and CMV disease (fever, leukopenia or organ involvement with CMV DNAemia >2000 copies/ml), measured using CMV viral load every month for first 3 months and then every 3 months for 1 year
7. Incidence of BK viremia ( >10000 copy/ml blood) and BK associated nephropathy, measured using BK virus plasma PCR every month for first 3 months then every 3 months

Overall trial start date

01/09/2016

Overall trial end date

01/09/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. First transplant
2. Cadaveric and living unrelated donor (age of cadaveric donor<50 years)
3. PRA negative (cytotoxicity)
4. Pretransplant anti-HLA negative (solid phase ELISA)
5. BMI <30
6. Age 18-65

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

60 in each group

Participant exclusion criteria

1. DGF (need for dialysis in first week)
2. SGF (serum creatinine > 3 mg/dl in day 3)

Recruitment start date

01/10/2016

Recruitment end date

01/04/2017

Locations

Countries of recruitment

Iran

Trial participating centre

Labbafinejad Hospital
9th Boostan Pasdaran Street
Tehran
2356987452
Iran

Sponsor information

Organisation

Urology, Nephrology Research Center

Sponsor details

9th Boostan
Pasdaran St
Tehran
3366339956
Iran

Sponsor type

University/education

Website

Funders

Funder type

Industry

Funder name

Sanofi

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

Results and Publications

Publication and dissemination plan

The trialists intend to publish the study in journals with high impact factors about 3 months after finishing the trial.

IPD sharing plan
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/12/2017

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes