Clinical trial NCT03582878: Sirolimus vs Mycophenolate With Tacrolimus in Simultaneous Pancreas and Kidney Transplantation
Official title: Effect of Sirolimus or Mycophenolate With Tacrolimus on Survival of Pancreas and Kidney Grafts in Type 1 Diabetic Recipients After Simultaneous Pancreas and Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 1
Lead sponsor: Institute for Clinical and Experimental Medicine
Sponsor class: OTHER_GOV
First posted: 2018-07-11
Enrollment: 238
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: This is prospective randomized open single center clinical study to compare effect of sirolimus vs mycophenolate tacrolimus based protocol on pancreas and kidney graft survival in simultaneous pancreas and kidney recipients.

Detailed description: MTOR (mammalian target of rapamycin) inhibitors represent group of immunosuppressive drugs with mechanism of T-cell blockade complementary to calcineurin inhibitors. The investigators presume that combination of sirolimus with tacrolimus will result in better survival of pancreatic and kidney grafts in simultaneous pancreas and kidney transplantations.

The study is proposed as a single-center extension of EUROSPK 002 trial originally started in 2004 by the EUROSPK Study Group. Recruitment of recipients started in 2004 with approval of EUROSPK 002. The patient recruitment has continued in a single center (Institute for Clinical and Experimental Medicine in Prague, Czech Republic) using the same inclusion and exclusion criteria. The recipients of primary kidney and pancreas transplantation have been randomized into 2 arms.

* In the intervention arm sirolimus is added to protocol at a dose of 5 mg immediately before transplantation, the dose is adjusted to maintained trough sirolimus trough levels between 5-10ng/ml.
* In the control arm mycophenolate mofetil was added to tacrolimus. Starting with 1g before transplantation, the dose has been increased to 1g bid afterwards.

Induction protocol at day 0. consists of ATG (antithymocyte globulin)induction 8mg/kg , Tacrolimus 0.05mg/kg, Methylprednisolone 125mg. Dosing of tacrolimus has been adjusted to maintain trough levels between 5-10ng/ml. ATG was administered at 3mg/kg on days 1.-3. Steroids have been gradually tapered from a dose of 20 mg prednison orally and withdrawn by 6w after transplantation.

Eligibility criteria: Inclusion Criteria:

* Type 1 diabetes mellitus
* End stage kidney failure
* Negative CDC crossmatch
* Female patients of childbearing age must have a negative pregnancy test
* Patient must have signed the Patient Informed Consent Form.
* Patient must receive a primary simultaneous pancreas/kidney (SPK) cadaver transplant,

Exclusion Criteria:

* Patient is pregnant or breastfeeding.
* Patient is allergic or intolerant to Mycophenolate Mofetil, Sirolimus, ATG, Tacrolimus
* Patient has malignancy or history of malignancy, with the exception of adequately treated localized squamous cell or basal cell carcinoma, without recurrence.
* Patient has been included in another clinical trial protocol for any investigational drug within 4 weeks prior to randomization.
* Patient has any form of substance abuse or psychiatric disorder or condition, which invalidate communication.
* Severe cardiac failure or severe liver failure diagnosed at the time of transplantation

Primary outcomes:
measure: Pancreas graft survival
timeFrame: 10 years
Secondary outcomes:
measure: Recipient survival
timeFrame: 10 years
measure: Wound healing time
timeFrame: 1year
measure: Kidney graft survival
timeFrame: 10 years
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: Institute for Clinical and Experimental Medicine
Study officials:
affiliation: Institute for Clinical and Experimental Medicine
name: Frantisek Saudek, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Girman P, Lipar K, Kocik M, Voska L, Koznarova R, Marada T, Lanska V, Saudek F. Sirolimus vs mycophenolate mofetil (MMF) in primary combined pancreas and kidney transplantation. Results of a long-term prospective randomized study. Am J Transplant. 2020 Mar;20(3):779-787. doi: 10.1111/ajt.15622. Epub 2019 Oct 23.