Kidney TransplantationPhase 4NCT00452361

Study Evaluating of Calcineurin Inhibitors Versus Sirolimus in Renal Allograft Recipient

A Phase 4 study testing Sirolimus+MMF or MPS or AZA+Steroid and Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid in people with Kidney Transplantation, run by Wyeth is now a wholly owned subsidiary of Pfizer at 1 site in Taiwan.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

This study will evaluate whether conversion from cyclosporine, a calcineurin inhibitor (CI) to sirolimus (SRL) results in improved long-term renal function without a negative impact on safety or immunosuppressive efficacy, and to further examine the potential of SRL to reduce the severity and/or progression of chronic… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Kidney Transplantation
What is being tested?: Sirolimus+MMF or MPS or AZA+Steroid and Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 31 participants
Where: 1 siteTaiwan
Study dates: Apr 2007to Aug 2008
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects must be at least 18 years of age.
Subjects who are 6 to 60 months after renal transplantation.
Subjects who have a stable graft function.

Who cannot join

Subjects with active major infection, including HIV, decreased platelets, elevated lipids, or multiple organ transplants.

Trial locations and contacts

1 site in 1 country.

Taiwan1 site

Study site
Select Cities

Other trials in Taiwan

About this study

Official title: A Randomized, Open-label, Comparative Evaluation of Conversion From Calcineurin Inhibitors to Sirolimus Versus Continued Use of Calcineurin Inhibitors in Renal Allograft Recipient

Read the detailed description

This open-label, randomized, parallel-group, comparative, outpatient study will be conducted in multiple centers in Taiwan.

The study will randomize approximately 120 patients. 80 patients will be randomized to the SRL therapy group (conversion from CI- to SRL-based immunosuppression: group A) and 40 patients to the CI therapy group (continued CI therapy: group B).

Dosage and Administration

SRL Therapy: At the time of randomization on day 1, each patient will have been receiving:

triple therapy with a CI (tacrolimus or CsA) that began at the time of transplantation or within 2 weeks thereafter AND
corticosteroids corresponding to a dosage range of 2.5 to 15 mg/day for prednisone or prednisolone (2 to 12 mg/day for methylprednisolone) or the alternate day equivalent for at least 12 weeks before randomization, PLUS
either MMF (minimum dose 500 mg/day)/MPS (minimum dose 360 mg/day) or AZA (minimum dose 50 mg/day) for at least 12 weeks before randomization.

SRL will be added to the immunosuppressive regimen for Group A. Group B will continue on this CI immunosuppressive regimen.

Conditions: Kidney Transplantation
Being tested: Sirolimus+MMF or MPS or AZA+Steroid, Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Sirolimus+MMF or MPS or AZA+SteroidDrug
Corticosteroids will be administered according to local practice, within a daily maintenance dosage range of 2.5 to15 mg for prednisone or prednisolone (2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.
Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+SteroidDrug
The maintenance dose of:
1. MMF will not exceed 1500 mg/day or PMS will not exceed 1080 mg/day
2. AZA will not exceed 75 mg/day
Thereafter, at the discretion of the investigator, MMF/MPS or AZA may be:
1. continued for the entire 104-week period of randomized therapy
2. subsequently discontinued
3. restarted after discontinuation

Study groups in NCT00452361
Study group	Role	What they receive
1	Experimental	Sirolimus therapy Receives: Drug: Sirolimus+MMF or MPS or AZA+Steroid
2	Active comparator	Calcineurin Inhibitor therapy (either cyclosporine or tacrolimus) Receives: Drug: Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Glomerular Filtration Rate (GFR) Change From Baseline
GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. GFR was calculated using Nankivell formula. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poor kidney function. A GFR <15 is consistent with kidney failure.
Measured: 104 weeks

Secondary outcomes (18)

Change in Glomerular Filtration Rate (GFR)
GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. GFR was calculated using Nankivell formula. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poor kidney function. A GFR <15 is consistent with kidney failure.
Measured: Baseline and Week 24
Change in Glomerular Filtration Rate (GFR)
GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. GFR was calculated using Nankivell formula. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poor kidney function. A GFR <15 is consistent with kidney failure.
Measured: Baseline and Week 52
Change in Glomerular Filtration Rate (GFR)
GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. GFR was calculated using Nankivell formula. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poor kidney function. A GFR <15 is consistent with kidney failure.
Measured: Baseline and Week 104
Patient and Graft Survival
Patient survival defined as participants living with or without a functioning graft. Graft survival defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.
Measured: Week 24
Patient and Graft Survival
Patient survival defined as participants living with or without a functioning graft. Graft survival defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.
Measured: Week 52
Patient and Graft Survival
Patient survival defined as participants living with or without a functioning graft. Graft survival defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.
Measured: Week 104
Change From Baseline in Diastolic Blood Pressure at Week 24
Value at Week 24 minus value at baseline.
Measured: Baseline and Week 24
Change From Baseline in Diastolic Blood Pressure at Week 52
Value at Week 52 minus value at baseline.
Measured: Baseline and Week 52
Change From Baseline in Diastolic Blood Pressure at Week 104
Value at Week 104 minus value at baseline.
Measured: Baseline and Week 104
Change From Baseline in Systolic Blood Pressure at Week 24
Value at Week 24 minus value at baseline.
Measured: Baseline and Week 24
Change From Baseline in Systolic Blood Pressure at Week 52
Value at Week 52 minus value at baseline.
Measured: Baseline and Week 52
Change From Baseline in Systolic Blood Pressure at Week 104
Value at Week 104 minus value at baseline.
Measured: Baseline and Week 104
Change From Baseline in the Severity and Progression of Biopsy-Confirmed Chronic Allograft Nephropathy (CAN) at Week 104
Measured: Baseline and Week 104
Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 52
Measured: Weeks 52
Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 104
Measured: Week 104
Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 24
Measured: Week 24
Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 52
Measured: Week 52
Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 104
Measured: Week 104

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2007Aug 2008

First posted27 Mar 2007 (estimated)
Study startApr 2007
Primary completionAug 2008
Study completionAug 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Kidney TransplantationStudies 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: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00452361
Sponsor's protocol ID: 0468H-101864
Status last verified: Jul 2012
First submitted: 23 Mar 2007
Last updated: 3 Sep 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Enrolling by invitation
Online Exercise Program for Transplant Patients: A Pilot Study
Kidney Transplantation, Physical Function
RecruitingPhase 2
A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant
Antibody-Mediated Rejection (AMR)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruitingEarly Phase 1
Biomarker-Guided Mycophenolate Mofetil Elimination in Low-Risk Older Adult Kidney Transplant Recipients
Kidney Transplant Recipient
Recruiting
Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Pediatric Kidney Disease, Transplant;Failure,Kidney

All Kidney Transplantation trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Open-label, Comparative Evaluation of Conversion From Calcineurin Inhibitors to Sirolimus Versus Continued Use of Calcineurin Inhibitors in Renal Allograft Recipient
ClinicalTrials.gov ID: NCT00452361
Acronym / sponsor ID: 0468H-101864
Conditions: Kidney Transplantation
Phase: Phase 4
Study type: Interventional
Recruitment status: Terminated
Enrolment: 31 participants (actual)
Lead sponsor: Wyeth is now a wholly owned subsidiary of PfizerIndustry (pharma, biotech, devices)
Study start: Apr 2007
Primary completion: Aug 2008 (actual)
Study completion: Aug 2008 (actual)
First posted: 27 Mar 2007 (estimated)
Results: Posted 3 Sep 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

This open-label, randomized, parallel-group, comparative, outpatient study will be conducted in multiple centers in Taiwan.

Dosage and Administration

SRL Therapy: At the time of randomization on day 1, each patient will have been receiving:

triple therapy with a CI (tacrolimus or CsA) that began at the time of transplantation or within 2 weeks thereafter AND
corticosteroids corresponding to a dosage range of 2.5 to 15 mg/day for prednisone or prednisolone (2 to 12 mg/day for methylprednisolone) or the alternate day equivalent for at least 12 weeks before randomization, PLUS
either MMF (minimum dose 500 mg/day)/MPS (minimum dose 360 mg/day) or AZA (minimum dose 50 mg/day) for at least 12 weeks before randomization.

SRL will be added to the immunosuppressive regimen for Group A. Group B will continue on this CI immunosuppressive regimen.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: Sirolimus+MMF or MPS or AZA+SteroidSirolimus therapy
2	Active comparator	Drug: Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+SteroidCalcineurin Inhibitor therapy (either cyclosporine or tacrolimus)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Subjects must be at least 18 years of age.
Subjects who are 6 to 60 months after renal transplantation.
Subjects who have a stable graft function.

Key exclusion criteria (1 listed)

Subjects with active major infection, including HIV, decreased platelets, elevated lipids, or multiple organ transplants.

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+MMF or MPS or AZA+SteroidCorticosteroids will be administered according to local practice, within a daily maintenance dosage range of 2.5 to15 mg for prednisone or prednisolone (2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Drug	1
Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+SteroidThe maintenance dose of: 1. MMF will not exceed 1500 mg/day or PMS will not exceed 1080 mg/day 2. AZA will not exceed 75 mg/day Thereafter, at the discretion of the investigator, MMF/MPS or AZA may be: 1. continued for the entire 104-week period of randomized therapy 2. subsequently discontinued 3. restarted after discontinuation	Drug	2

Primary outcome

Change in Glomerular Filtration Rate (GFR) Change From Baseline
Time frame: 104 weeks
GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. GFR was calculated using Nankivell formula. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poor kidney function. A GFR <15 is consistent with kidney failure.

18 secondary outcomes

Change in Glomerular Filtration Rate (GFR)
Time frame: Baseline and Week 24
Change in Glomerular Filtration Rate (GFR)
Time frame: Baseline and Week 52
Change in Glomerular Filtration Rate (GFR)
Time frame: Baseline and Week 104
Patient and Graft Survival
Time frame: Week 24
Patient and Graft Survival
Time frame: Week 52
Patient and Graft Survival
Time frame: Week 104
Change From Baseline in Diastolic Blood Pressure at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Diastolic Blood Pressure at Week 52
Time frame: Baseline and Week 52
Change From Baseline in Diastolic Blood Pressure at Week 104
Time frame: Baseline and Week 104
Change From Baseline in Systolic Blood Pressure at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Systolic Blood Pressure at Week 52
Time frame: Baseline and Week 52
Change From Baseline in Systolic Blood Pressure at Week 104
Time frame: Baseline and Week 104
Change From Baseline in the Severity and Progression of Biopsy-Confirmed Chronic Allograft Nephropathy (CAN) at Week 104
Time frame: Baseline and Week 104
Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 52
Time frame: Weeks 52
Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 104
Time frame: Week 104
Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 24
Time frame: Week 24
Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 52
Time frame: Week 52
Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 104
Time frame: Week 104

Results and safety

Results posted to the registry on 3 Sep 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sirolimus (SRL)	21	0
Calcineurin Inhibitor (CI)	10	0

Primary outcome: Change in Glomerular Filtration Rate (GFR) Change From Baseline

Time frame: 104 weeks

Population analysed: No patients completed 104 weeks and therefore no data were available for efficacy analysis.

18 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sirolimus (SRL)	6 of 21 (28.6%)	78 of 21 (371.4%)	Not reported
Calcineurin Inhibitor (CI)	2 of 10 (20%)	18 of 10 (180%)	Not reported

Limitations and caveats (from the sponsor): Study terminated early due to difficulties in enrolling qualified patients. No patients completed 104 weeks (primary outcome); a few completed 60 weeks. Insufficient data were available for efficacy analyses.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Kidney Transplantation

Enrolling by invitation
Online Exercise Program for Transplant Patients: A Pilot Study
Kidney Transplantation, Physical Function
RecruitingPhase 2
A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant
Antibody-Mediated Rejection (AMR)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruitingEarly Phase 1
Biomarker-Guided Mycophenolate Mofetil Elimination in Low-Risk Older Adult Kidney Transplant Recipients
Kidney Transplant Recipient
Recruiting
Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Pediatric Kidney Disease, Transplant;Failure,Kidney

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.

Medical Monitor study director

Wyeth is now a wholly owned subsidiary of Pfizer

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 3 inclusion and 1 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: stopped early, as of the sponsor's last update on 3 Sep 2012. 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 Taiwan. 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?

Yes. Results are posted in the registry (first posted 3 Sep 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change in Glomerular Filtration Rate (GFR) Change From Baseline (time frame: 104 weeks). 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 NCT00452361.

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 3 Sep 2012.