Sirolimus vs Mycophenolate With Tacrolimus in Simultaneous Pancreas and Kidney Transplantation

Diabetes Mellitus, Type 1 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03582878
• Other study ID #: SiroMMFStudy 1
• Status: Completed
• Phase: Phase 4
• Start date: January 1, 2004
• Est. completion date: January 1, 2019

Study information

• Verified date: April 2021
• Source: Institute for Clinical and Experimental Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 238
• Est. completion date: January 1, 2019
• Est. primary completion date: January 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1

Intervention

Drug:
• Sirolimus Oral Product
Oral form of sirolimus, daily dosing to achieve target trough levels between 5-10ng/ml since 1.day of transplantation
• Mycophenolate Mofetil
Mycophenolate Mofetil dosing 1g before transplantation and 1g bid afterwards

Locations

Country	Name	City	State
Czechia	Institute for Clinical and Experimental Medicine	Prague

Sponsors (1)

Lead Sponsor	Collaborator
Institute for Clinical and Experimental Medicine

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pancreas graft survival	Number of failed pancreatic grafts, failure is defined as graft removal, death, retransplantation or return to intensified insulin regimen.	10 years
Secondary	Recipient survival	Long-term recipient survival evaluated with Kaplan-Meyer method	10 years
Secondary	Wound healing time	The number of days from transplantation to date of completely healed wound	1year
Secondary	Kidney graft survival	Number of failed kidneys evaluated with Kaplan-Meyer method. Failure defined as return to dialysis, death, retransplantation or graft removal	10 years