A randomized multicenter trial to assess the efficacy of a combined therapy with Sirolimus (Rapamune®), MMF (Cellsept®) and corticosteroids after early elimination of cyclosporin compared to a standard immunosuppression with cyclosporin, MMF and corticosteroids in patients after kidney transplantation

ISRCTN	ISRCTN74429508
DOI	https://doi.org/10.1186/ISRCTN74429508
Protocol serial number	00/03 - A2, V 12.04.2005
Sponsor	University of Munich - Department of Surgery (Germany)
Funder	Wyeth Pharmaceuticals

Submission date: 20/06/2005
Registration date: 04/10/2005
Last edited: 07/07/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Surgery

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Markus Guba
Scientific

Dept of Surgery
Hospital of the University of Munich (LMU)
Klinikum Grosshadern
Marchioninistr. 15
Munich
81377
Germany

Phone	+49 89 7095 3573
Email	markus.guba@med.uni-muenchen.de

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Multi-centre
Scientific title	-
Study acronym	SMART
Study objectives	Early conversion to a calcineurin-inhibitor-free protocol with Sirolimus (Rapamune®) in combination with MMF (Cellcept®) and corticosteroids is superior to a standard protocol with Cyclosporin (Sandimmun®) in combination with MMF (Cellcept®) and corticosteroids at the level of graft-function at 12 months.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Terminal renal failure
Intervention	Patients with terminal renal failure undergoing renal transplantation. After an initial immunosuppression with Cyclosporin, MMF and Steroids for 10-24 days, patients in the study group A are converted to Sirolimus, MMF and Steroids. Patients in the control group continue on Cyclosporin, MMF and Steroids.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Serolimus (Rapamune®), MMF (Cellsept®), cyclosporin (Sandimmun®), corticosteroids
Primary outcome measure(s)	Graft function at 12 months defined as creatinine clearance calculated according to the Cockroft-Gault formula and serum creatinine level.
Key secondary outcome measure(s)	1. Incidence of biopsy proven acute rejection episodes according to Banff 97 classification 2. Patient and graft survival at 12 months 3. Incidence of treatment failure defined as: a. Switch to another immunosuppressive regimen b. Continuing removal of a single immunosuppressant (except MP) c. Switch to another immunosuppressive regimen because of side effects 4. Incidence of infections 5. Incidence of malignancies 6. Incidence of new onset of hypertension 7. Incidence of side effects (e.g. metabolic disorders, others)
Completion date	31/03/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	140
Key inclusion criteria	1. Male or female patients between 18 and 60 years of age 2. Primary or secondary kidney allograft recipients (PRA <30%) 3. No requirement for dialysis since three days before randomization 4. Women of childbearing potential must have a negative qualitative pregnancy test before Sirolimus administration and agree to use a medically acceptable method of contraception throughout the treatment period and for three months following discontinuation of Sirolimus. Any woman becoming pregnant during the treatment period must discontinue Sirolimus treatment 5. Signed and dated informed consent
Key exclusion criteria	1. Multiorgan transplant recipients 2. Cold ischemia time >36 hours 3. PRA > 30% 4. Postoperative technical complications necessitating re operation (e.g. kidney artery stenosis) or wound healing disturbances (e.g. voluminous lymphoceles) 5. Recipients of A-B-0 incompatible grafts 6. Body mass index >32 7. Patients with cardiac infarction within six months before study entry or actual unstable coronary heart disease 8. Total number of neutrophile granulocytes <1,500/mm^3 or leucocytes <2,500/mm^3 at screening 9. Patients with severe hepatic impairment (glutamic-oxaloacetic transaminase [GOT], glutamic-pyruvic transaminase [GPT], total bilirubin above three times the norm) 10. Total cholesterol >300 mg/dl and triglycerides >400 mg/dl (even under lipid lowering treatment) 11. Patients with severe intestinal disorders or other diseases significantly influencing resorption, distribution, metabolism and elimination of study medication (except diabetes) at the discretion of the investigator 12. Recipients positive for hepatitis B surface antigens or human immunodeficiency virus (HIV), organs from donors positive for hepatitis B surface antigens or HIV 13. Active malignancies within two years before study entry with the exception of squamous cell carcinoma and basal cell carcinoma of the skin 14. Patients with active systemic infections or significant coagulopathy or requirement of long term anticoagulation therapy after transplantation 15. Use of any investigational drug within four weeks before study entry 16. Known intolerability of Cyclosporine, Sirolimus, MMF or other medication required after transplantation 17. Patients with diseases which potentially could impair study performance at the discretion of the investigator 18. Pregnancy and lactation 19. Refusal to sign informed consent form 20. Patients with ongoing requirement of dialysis at time of randomization
Date of first enrolment	01/03/2005
Date of final enrolment	31/03/2007

Locations

Countries of recruitment

Germany

Study participating centre

Dept of Surgery

Munich
81377
Germany

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		27/07/2010	07/07/2021	Yes	No

Editorial Notes

07/07/2021: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.