Comparison of de novo sirolimus plus tacrolimus with tacrolimus plus mycofenolic acid in renal transplantation
| ISRCTN | ISRCTN19991928 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN19991928 |
| Secondary identifying numbers | N/A |
- Submission date
- 15/08/2016
- Registration date
- 15/06/2017
- Last edited
- 17/01/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Urological and Genital Diseases
Plain English summary of protocol
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
Contact information
Scientific
9th Boostan
Pasdaran St
Tehran
5546859685
Iran
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Comparison of de novo sirolimus plus tacrolimus with tacrolimus plus mycofenolic acid in renal transplantation: a randomized clinical trial |
| Study objectives | Sirolimus plus tacrolimus has the same effect as tacrolimus plus mycofenolic acid in renal transplantation outcomes. |
| Ethics approval(s) | Shahid Beheshti University of Medical Sciences, 15/08/2016, ref: IR.SBMU.UNRC.1394.25 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Thymoglobulin, mycophenolic acid, tacrolimus, prednisolone, ganciclovir, valganciclovir, sirolimus |
| Primary outcome measure | 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 study start date | 01/09/2016 |
| Completion date | 01/09/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | 60 in each group |
| Key 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 |
| Key exclusion criteria | 1. DGF (need for dialysis in first week) 2. SGF (serum creatinine > 3 mg/dl in day 3) |
| Date of first enrolment | 01/10/2016 |
| Date of final enrolment | 01/04/2017 |
Locations
Countries of recruitment
- Iran
Study participating centre
Pasdaran Street
Tehran
2356987452
Iran
Sponsor information
University/education
Urology Nephrology Research Center
9th Boostan/Pasdaran St
Tehran
3366339956
Iran
| Website | http://en.sbu.ac.ir/sitepages/home.aspx |
|---|---|
"ROR" |
https://ror.org/034m2b326 |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- sanofi-aventis, Sanofi US, Sanofi-Aventis U.S. LLC, Sanofi U.S.
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/12/2017 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| 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. |
Editorial Notes
17/01/2020: Internal review.
