Kidney TransplantationPhase 4DESIRENCT02062892
Differentiating Everolimus Versus Sirolimus in Combination With Calcineurin Inhibitors in Kidney Transplant Patients
A Phase 4 study testing Everolimus and Sirolimus in people with Kidney Transplantation, run by University of Colorado, Denver.
Trial summary
The investigators hypothesize that switching kidney transplant patients on tacrolimus/sirolimus long-term maintenance immunosuppressive drug regimens to tacrolimus/everolimus, will not only be safe, but will lead to better kidney function than patients staying on tacrolimus/sirolimus due to the lower potential of… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- Everolimus and Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2013to Jun 2014
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Kidney transplant patients ≥ 3 months after transplantation. De novo patients on sirolimus and tacrolimus as well as patients switched to tacrolimus and sirolimus will be eligible as long as they have received this drug combination for at least 2 months.
- Immunosuppressive drug regimen based on tacrolimus and sirolimus
- 18-70 years of age
- calculated glomerular filtration rate≥ 30 mL/min/ 1.73m2 as calculated using the abbreviated Modification of Diet in Renal Disease formula
- Ability and willingness to provide written informed consent and adhere to study regimen.
- Patients who are able to take oral medication at time of randomization.
Who cannot join
- Patients switched to tacrolimus and sirolimus due to clinically relevant nephrotoxicity of the previous immunosuppressive drug regimen,
- Patients with an abnormal liver profile such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or total bilirubin > 3 x upper limit of normal at time of randomization
- Patients with severe total hypercholesterolemia (> 350 mg/dL; > 9 mmol/L) or total hypertriglyceridemia (> 500 mg/dL; > 5.6 mmol/L). Patients on lipid lowering treatment with controlled hyperlipidemia are acceptable.
- Patients who tested positive for HIV, Hepatitis C or Hepatitis B surface antigen.
- An episode of acute rejection that required antibody therapy or more than one steroid sensitive episode of acute rejection prior to enrollment.
- Spot urine protein/creatinine ratio > 1g/24h at the time of randomization
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- Multi-organ transplants
- Patients with platelet count < 50,000
- Patients with an absolute neutrophil count of < 1,000 or white blood cells of <2,000 at time of enrollment
- Patients with hemoglobin < 6g/dL
- Patients with clinically significant systemic infections requiring active use of IV antibiotics, anti-virales, or anti-fungals. Prophylactic use of anti-virales will be acceptable.
- Pregnancy or inability of practicing acceptable contraceptive measures.
- Patients who have any surgical or medical condition, such as severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus, which in the opinion of the investigator might significantly alter the absorption, distribution, metabolism and/or excretion of study medication.
About this study
Official title: Differentiating Sirolimus and Everolimus in Combination With Calcineurin Inhibitors in Long-term Maintenance of Kidney Transplant Patients - The Effects on Vascular Endothelial and Kidney Function. The DESIRE Study.
The investigators hypothesize that switching kidney transplant patients on tacrolimus/sirolimus long-term maintenance immunosuppressive drug regimens to tacrolimus/everolimus, will not only be safe, but will lead to better kidney function than patients staying on tacrolimus/sirolimus due to the lower potential of everolimus to enhance calcineurin inhibitors toxicity and/or its ability to even reverse some of the negative effects of calcineurin inhibitors on vascular endothelial and kidney function. To test this hypothesis vascular endothelial biomarkers will be analyzed in blood plasma samples and kidney dysfunction biomarkers in urine samples via liquid chromatography tandem mass spectrometry to evaluate whether switching kidney transplant patients on tacrolimus/sirolimus to tacrolimus/everolimus will lead to better kidney and endothelial function after one year and two years.
- Conditions
- Kidney Transplantation
- Being tested
- Everolimus, Sirolimus
- Keywords
- everolimus, sirolimus, tacrolimus, vascular endothelial function, kidney, Transplantation, biomarkers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called Zortress
Patients will be stable kidney transplant patients who are receiving an immunosuppressive drug regimen based on tacrolimus and sirolimus. 24 hours after the last sirolimus dose, the patients randomized to the tacrolimus/everolimus arm of the study will be switched from sirolimus to everolimus 1:1 (same sirolimus as everolimus dose). Everolimus doses will be adjusted so that trough blood concentrations are within 3-8 ng/mL. In detail: Tacrolimus (Prograf or FDA approved generic 0.5 mg, 1 mg or 5 mg capsules, twice a day) in combination with Everolimus (Zortress, 0.25, 0.5 and 0.75 tablets).
SirolimusDrug
Patients will be stable kidney transplant patients who are receiving an immunosuppressive drug regimen based on tacrolimus and sirolimus. 24 hours after the last sirolimus dose, the patients randomized to the tacrolimus/sirolimus arm of the study will remain on tacrolimus/sirolimus. In detail: Tacrolimus (Prograf or FDA approved generic 0.5 mg, 1 mg or 5 mg capsules, once a day) in combination with Sirolimus (Rapamune, 0.5, 1, and 2mg tablets).
| Study group | Role | What they receive |
|---|---|---|
| Everolimus / Tacrolimus | Experimental | Patients will be stable kidney transplant patients who are receiving an immunosuppressive drug regimen based on tacrolimus and sirolimus. 24 hours after the last sirolimus dose, the patients randomized to the tacrolimus/everolimus arm of the study will be switched from sirolimus to everolimus 1:1 (same sirolimus as everolimus dose). Everolimus doses will be adjusted so that trough blood concentrations are within 3-8 ng/mL. In detail: Tacrolimus (Prograf or FDA approved generic 0.5 mg, 1 mg or 5 mg capsules, twice a day) in combination with Everolimus (Zortress, 0.25, 0.5 and 0.75 tablets). Receives: Drug: Everolimus |
| Sirolimus / Tacrolimus | Active comparator | Patients will be stable kidney transplant patients who are receiving an immunosuppressive drug regimen based on tacrolimus and sirolimus. 24 hours after the last sirolimus dose, the patients randomized to the tacrolimus/sirolimus arm of the study will remain on tacrolimus/sirolimus. In detail: Tacrolimus (Prograf or FDA approved generic 0.5 mg, 1 mg or 5 mg capsules, once a day) in combination with Sirolimus (Rapamune, 0.5, 1, and 2mg tablets). Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Creatinine Outcome Measure (1)
Kidney function outcome markers will be assessed one year after kidney transplant
Measured: 1 year
Calculated Glomerular Filtration Rate (1)
Kidney function outcome markers will be assessed one year after kidney transplant
Measured: 1 year
Calculated Glomerular Filtration Rate (2)
Kidney function outcome markers will be assessed two years after kidney transplant
Measured: 2 years
Kidney Injury Molecule-1 (1)
Kidney function outcome markers will be assessed one year after kidney transplant
Measured: 1 year
Kidney Injury Molecule-1 (2)
Kidney function outcome markers will be assessed two years after kidney transplant
Measured: 2 years
S-Adenosylhomocysteine Hydrolase (1)
Kidney function outcome markers will be assessed one year after kidney transplant
Measured: 1 year
S-Adenosylhomocysteine Hydrolase (2)
Kidney function outcome markers will be assessed two years after kidney transplant
Measured: 2 years
S-Adenosylmethionine (1)
Kidney function outcome markers will be assessed one year after kidney transplant
Measured: 1 year
S-Adenosylmethionine (2)
Kidney function outcome markers will be assessed two years after kidney transplant
Measured: 2 years
Creatinine Outcome Measure (2)
Kidney function outcome markers will be assessed two years after kidney transplant
Measured: 2 years
Secondary outcomes (10)
12-Hydroxyeicosatetraenoic acid (1)
Vascular endothelial dysfunction outcome markers will be assessed one year after kidney transplant
Measured: 1 year
12-Hydroxyeicosatetraenoic acid (2)
Vascular endothelial dysfunction outcome markers will be assessed two years after kidney transplant
Measured: 2 years
20-Hydroxyeicosatetraenoic acid (1)
Vascular endothelial dysfunction outcome markers will be assessed one year after kidney transplant
Measured: 1 year
20-Hydroxyeicosatetraenoic acid (2)
Vascular endothelial dysfunction outcome markers will be assessed two years after kidney transplant
Measured: 2 years
18- Hydroxyeicosapentaenoic acid (1)
Vascular endothelial dysfunction outcome markers will be assessed one year after kidney transplant
Measured: 1 year
18- Hydroxy- eicosapentaenoic acid (2)
Vascular endothelial dysfunction outcome markers will be assessed two years after kidney transplant
Measured: 2 years
Ornithine (1)
Vascular endothelial dysfunction outcome markers will be assessed one year after kidney transplant
Measured: 1 year
Ornithine (2)
Vascular endothelial dysfunction outcome markers will be assessed two years after kidney transplant
Measured: 2 years
Arginine (1)
Vascular endothelial dysfunction outcome markers will be assessed one year after kidney transplant
Measured: 1 year
Arginine (2)
Vascular endothelial dysfunction outcome markers will be assessed one year after kidney transplant
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2014 (estimated)
- Study startDec 2013
- Primary completionJun 2014
- Study completionJun 2014
Why it stopped: Patients meeting the inclusion/ exclusion criteria did not agree to participate. It became obvious that recruitment goals could not be met.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Laurence Chan, MD, PhD, Principal investigator, University of Colorado, DenverClifford Miles, MD, MS, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02062892
- Sponsor's protocol ID
- 13-1583
- Other IDs
- CRAD001AUS196T
- Acronym
- DESIRE
- Status last verified
- Dec 2014
- First submitted
- 11 Feb 2014
- Last updated
- 2 Dec 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Differentiating Sirolimus and Everolimus in Combination With Calcineurin Inhibitors in Long-term Maintenance of Kidney Transplant Patients - The Effects on Vascular Endothelial and Kidney Function. The DESIRE Study.
- ClinicalTrials.gov ID
- NCT02062892
- Acronym / sponsor ID
- DESIRE / 13-1583
- Conditions
- Kidney Transplantation
- Keywords
- everolimus, sirolimus, tacrolimus, vascular endothelial function, kidney, Transplantation, biomarkers
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Patients meeting the inclusion/ exclusion criteria did not agree to participate. It became obvious that recruitment goals could not be met.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Dec 2013
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 14 Feb 2014 (estimated)
- 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.
The investigators hypothesize that switching kidney transplant patients on tacrolimus/sirolimus long-term maintenance immunosuppressive drug regimens to tacrolimus/everolimus, will not only be safe, but will lead to better kidney function than patients staying on tacrolimus/sirolimus due to the lower potential of everolimus to enhance calcineurin inhibitors toxicity and/or its ability to even reverse some of the negative effects of calcineurin inhibitors on vascular endothelial and kidney function. To test this hypothesis vascular endothelial biomarkers will be analyzed in blood plasma samples and kidney dysfunction biomarkers in urine samples via liquid chromatography tandem mass spectrometry to evaluate whether switching kidney transplant patients on tacrolimus/sirolimus to tacrolimus/everolimus will lead to better kidney and endothelial function after one year and two years.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus / Tacrolimus | Experimental | Drug: EverolimusPatients will be stable kidney transplant patients who are receiving an immunosuppressive drug regimen based on tacrolimus and sirolimus. 24 hours after the last sirolimus dose, the patients randomized to the tacrolimus/everolimus arm of the study will be switched from sirolimus to everolimus 1:1 (same sirolimus as everolimus dose). Everolimus doses will be adjusted so that trough blood concentrations are within 3-8 ng/mL. In detail: Tacrolimus (Prograf or FDA approved generic 0.5 mg, 1 mg or 5 mg capsules, twice a day) in combination with Everolimus (Zortress, 0.25, 0.5 and 0.75 tablets). |
| Sirolimus / Tacrolimus | Active comparator | Drug: SirolimusPatients will be stable kidney transplant patients who are receiving an immunosuppressive drug regimen based on tacrolimus and sirolimus. 24 hours after the last sirolimus dose, the patients randomized to the tacrolimus/sirolimus arm of the study will remain on tacrolimus/sirolimus. In detail: Tacrolimus (Prograf or FDA approved generic 0.5 mg, 1 mg or 5 mg capsules, once a day) in combination with Sirolimus (Rapamune, 0.5, 1, and 2mg tablets). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Kidney transplant patients ≥ 3 months after transplantation. De novo patients on sirolimus and tacrolimus as well as patients switched to tacrolimus and sirolimus will be eligible as long as they have received this drug combination for at least 2 months.
- Immunosuppressive drug regimen based on tacrolimus and sirolimus
- 18-70 years of age
- calculated glomerular filtration rate≥ 30 mL/min/ 1.73m2 as calculated using the abbreviated Modification of Diet in Renal Disease formula
- Ability and willingness to provide written informed consent and adhere to study regimen.
Key exclusion criteria (13 listed)
- Patients switched to tacrolimus and sirolimus due to clinically relevant nephrotoxicity of the previous immunosuppressive drug regimen,
- Patients with an abnormal liver profile such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or total bilirubin > 3 x upper limit of normal at time of randomization
- Patients with severe total hypercholesterolemia (> 350 mg/dL; > 9 mmol/L) or total hypertriglyceridemia (> 500 mg/dL; > 5.6 mmol/L). Patients on lipid lowering treatment with controlled hyperlipidemia are acceptable.
- Patients who tested positive for HIV, Hepatitis C or Hepatitis B surface antigen.
- An episode of acute rejection that required antibody therapy or more than one steroid sensitive episode of acute rejection prior to enrollment.
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 |
|---|---|---|
| EverolimusAlso: ZortressPatients will be stable kidney transplant patients who are receiving an immunosuppressive drug regimen based on tacrolimus and sirolimus. 24 hours after the last sirolimus dose, the patients randomized to the tacrolimus/everolimus arm of the study will be switched from sirolimus to everolimus 1:1 (same sirolimus as everolimus dose). Everolimus doses will be adjusted so that trough blood concentrations are within 3-8 ng/mL. In detail: Tacrolimus (Prograf or FDA approved generic 0.5 mg, 1 mg or 5 mg capsules, twice a day) in combination with Everolimus (Zortress, 0.25, 0.5 and 0.75 tablets). | Drug | Everolimus / Tacrolimus |
| SirolimusPatients will be stable kidney transplant patients who are receiving an immunosuppressive drug regimen based on tacrolimus and sirolimus. 24 hours after the last sirolimus dose, the patients randomized to the tacrolimus/sirolimus arm of the study will remain on tacrolimus/sirolimus. In detail: Tacrolimus (Prograf or FDA approved generic 0.5 mg, 1 mg or 5 mg capsules, once a day) in combination with Sirolimus (Rapamune, 0.5, 1, and 2mg tablets). | Drug | Sirolimus / Tacrolimus |
Primary outcome
Creatinine Outcome Measure (1)
Time frame: 1 year
Kidney function outcome markers will be assessed one year after kidney transplant
Calculated Glomerular Filtration Rate (1)
Time frame: 1 year
Kidney function outcome markers will be assessed one year after kidney transplant
Calculated Glomerular Filtration Rate (2)
Time frame: 2 years
Kidney function outcome markers will be assessed two years after kidney transplant
Kidney Injury Molecule-1 (1)
Time frame: 1 year
Kidney function outcome markers will be assessed one year after kidney transplant
Kidney Injury Molecule-1 (2)
Time frame: 2 years
Kidney function outcome markers will be assessed two years after kidney transplant
S-Adenosylhomocysteine Hydrolase (1)
Time frame: 1 year
Kidney function outcome markers will be assessed one year after kidney transplant
S-Adenosylhomocysteine Hydrolase (2)
Time frame: 2 years
Kidney function outcome markers will be assessed two years after kidney transplant
S-Adenosylmethionine (1)
Time frame: 1 year
Kidney function outcome markers will be assessed one year after kidney transplant
S-Adenosylmethionine (2)
Time frame: 2 years
Kidney function outcome markers will be assessed two years after kidney transplant
Creatinine Outcome Measure (2)
Time frame: 2 years
Kidney function outcome markers will be assessed two years after kidney transplant
10 secondary outcomes
12-Hydroxyeicosatetraenoic acid (1)
Time frame: 1 year
12-Hydroxyeicosatetraenoic acid (2)
Time frame: 2 years
20-Hydroxyeicosatetraenoic acid (1)
Time frame: 1 year
20-Hydroxyeicosatetraenoic acid (2)
Time frame: 2 years
18- Hydroxyeicosapentaenoic acid (1)
Time frame: 1 year
18- Hydroxy- eicosapentaenoic acid (2)
Time frame: 2 years
Ornithine (1)
Time frame: 1 year
Ornithine (2)
Time frame: 2 years
Arginine (1)
Time frame: 1 year
Arginine (2)
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2014.
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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.
Laurence Chan, MD, PhD principal investigator
University of Colorado, Denver
Clifford Miles, MD, MS principal investigator
University of Nebraska
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Everolimus and Sirolimus in people with Kidney Transplantation, run by University of Colorado, Denver.
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 13 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: withdrawn, as of the sponsor's last update on 2 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
Creatinine Outcome Measure (1) (time frame: 1 year). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Dec 2014; AzTrials last refreshed its copy on 8 Nov 2026.