Diabetes Mellitus, Type 1Phase 4NCT03582878
Sirolimus vs Mycophenolate With Tacrolimus in Simultaneous Pancreas and Kidney Transplantation
A Phase 4 study testing Sirolimus Oral Product and Mycophenolate Mofetil in people with Diabetes Mellitus, Type 1, run by Institute for Clinical and Experimental Medicine at 1 site in Czechia.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Sirolimus Oral Product and Mycophenolate Mofetil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 238 participants
- Where
- 1 siteCzechia
- Study dates
- 1 Jan 2004to 1 Jan 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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,
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Sirolimus Oral Product, Mycophenolate Mofetil
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sirolimus Oral ProductDrug
Also called Rapamune
Oral form of sirolimus, daily dosing to achieve target trough levels between 5-10ng/ml since 1.day of transplantation
Also called CellCept
Mycophenolate Mofetil dosing 1g before transplantation and 1g bid afterwards
| Study group | Role | What they receive |
|---|---|---|
| mycophenolate mofetil | Active comparator | mycophenolate mofetil dosing 1g before transplantation and 1g bid afterwards Receives: Drug: Mycophenolate Mofetil |
| Sirolimus | Experimental | Sirolimus oral product Dosing 5mg orally 2-6h before transplantation Target trough levels between 5-10ng/ml Receives: Drug: Sirolimus Oral Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pancreas graft survival
Number of failed pancreatic grafts, failure is defined as graft removal, death, retransplantation or return to intensified insulin regimen.
Measured: 10 years
Secondary outcomes (3)
Recipient survival
Long-term recipient survival evaluated with Kaplan-Meyer method
Measured: 10 years
Wound healing time
The number of days from transplantation to date of completely healed wound
Measured: 1year
Kidney graft survival
Number of failed kidneys evaluated with Kaplan-Meyer method. Failure defined as return to dialysis, death, retransplantation or graft removal
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2018
- Study start1 Jan 2004
- Primary completion1 Jan 2019
- Study completion1 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 238 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute for Clinical and Experimental Medicine
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Frantisek Saudek, Institute for Clinical and Experimental Medicine
- Investigators
- Frantisek Saudek, MD, Principal investigator, Institute for Clinical and Experimental Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03582878
- Sponsor's protocol ID
- SiroMMFStudy 1
- Status last verified
- Apr 2021
- First submitted
- 25 Apr 2018
- Last updated
- 26 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31561278
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03582878
- Acronym / sponsor ID
- SiroMMFStudy 1
- Conditions
- Diabetes Mellitus, Type 1
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 238 participants (actual)
- Lead sponsor
- Institute for Clinical and Experimental MedicineOther government
- Study start
- 1 Jan 2004 (actual)
- Primary completion
- 1 Jan 2019 (actual)
- Study completion
- 1 Jan 2019 (actual)
- First posted
- 11 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| mycophenolate mofetil | Active comparator | Drug: Mycophenolate Mofetilmycophenolate mofetil dosing 1g before transplantation and 1g bid afterwards |
| Sirolimus | Experimental | Drug: Sirolimus Oral ProductSirolimus oral product Dosing 5mg orally 2-6h before transplantation Target trough levels between 5-10ng/ml |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sirolimus Oral ProductAlso: RapamuneOral form of sirolimus, daily dosing to achieve target trough levels between 5-10ng/ml since 1.day of transplantation | Drug | Sirolimus |
| Mycophenolate MofetilAlso: CellCeptMycophenolate Mofetil dosing 1g before transplantation and 1g bid afterwards | Drug | mycophenolate mofetil |
Primary outcome
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.
3 secondary outcomes
Recipient survival
Time frame: 10 years
Wound healing time
Time frame: 1year
Kidney graft survival
Time frame: 10 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2021.
- Derived from this study: PubMed 31561278Girman 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frantisek Saudek, MD principal investigator
Institute for Clinical and Experimental Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sirolimus Oral Product and Mycophenolate Mofetil in people with Diabetes Mellitus, Type 1, run by Institute for Clinical and Experimental Medicine at 1 site in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pancreas graft survival (time frame: 10 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03582878, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2021.