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Sirolimus vs Mycophenolate With Tacrolimus in Simultaneous Pancreas and Kidney Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03582878
Recruitment Status : Completed
First Posted : July 11, 2018
Last Update Posted : April 26, 2021
Sponsor:
Information provided by (Responsible Party):
Frantisek Saudek, Institute for Clinical and Experimental Medicine

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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: Sirolimus Oral Product Drug: Mycophenolate Mofetil Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 238 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 1, 2004
Actual Primary Completion Date : January 1, 2019
Actual Study Completion Date : January 1, 2019


Arm Intervention/treatment
Active Comparator: mycophenolate mofetil
mycophenolate mofetil dosing 1g before transplantation and 1g bid afterwards
Drug: Mycophenolate Mofetil
Mycophenolate Mofetil dosing 1g before transplantation and 1g bid afterwards
Other Name: CellCept

Experimental: Sirolimus
Sirolimus oral product Dosing 5mg orally 2-6h before transplantation Target trough levels between 5-10ng/ml
Drug: Sirolimus Oral Product
Oral form of sirolimus, daily dosing to achieve target trough levels between 5-10ng/ml since 1.day of transplantation
Other Name: Rapamune




Primary Outcome Measures :
  1. Pancreas graft survival [ Time Frame: 10 years ]
    Number of failed pancreatic grafts, failure is defined as graft removal, death, retransplantation or return to intensified insulin regimen.


Secondary Outcome Measures :
  1. Recipient survival [ Time Frame: 10 years ]
    Long-term recipient survival evaluated with Kaplan-Meyer method

  2. Wound healing time [ Time Frame: 1year ]
    The number of days from transplantation to date of completely healed wound

  3. Kidney graft survival [ Time Frame: 10 years ]
    Number of failed kidneys evaluated with Kaplan-Meyer method. Failure defined as return to dialysis, death, retransplantation or graft removal



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03582878


Locations
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Czechia
Institute for Clinical and Experimental Medicine
Prague, Czechia, 14021
Sponsors and Collaborators
Institute for Clinical and Experimental Medicine
Investigators
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Principal Investigator: Frantisek Saudek, MD Institute for Clinical and Experimental Medicine
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Frantisek Saudek, professor, Institute for Clinical and Experimental Medicine
ClinicalTrials.gov Identifier: NCT03582878    
Other Study ID Numbers: SiroMMFStudy 1
First Posted: July 11, 2018    Key Record Dates
Last Update Posted: April 26, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Mycophenolic Acid
Sirolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs