Study Comparing Effect On Carotid Atherosclerosis Following Conversion From Tacrolimus To Sirolimus Post-Transplant In Kidney Transplant Patients

NCT00311311 | Terminated Phase 3 Results

• 1 other identifier: 0468H1-319
• Study Type: interventional
• Target: 72
• Locations: 2 countries
• Sites: 8

Brief Summary

The purpose of this study is to determine whether immunosuppression by tacrolimus, mycophenolate mofetil, and prednisone compared to conversion to sirolimus, mycophenolate mofetil, and prednisone affect the progression of atherosclerosis in renal transplant recipients.

Conditions

Atherosclerosis; Kidney Failure

Keywords

Kidney transplant; Renal transplant; Immunosuppression; Atherosclerosis; Graft Rejection

Outcome Measures

Primary Outcomes (2)

• Annual Change Rate in Total Plaque Volume (TPV) From Pre-conversion Baseline to 12 Months Post-transplant

  Within-subject annual change rate in TPV in the left and right distal common carotid arteries from the pre-conversion baseline to 12 months post kidney transplant as determined by ultrasound. Annual change rate equals (=) (TPV at month 12 post-transplant minus \[-\] TPV at pre-conversion baseline) divided (/) by imaging interval in years. TPV is the sum of assessment in left and right distal common carotid arteries.

  Pre-conversion baseline and 12 months post-transplant

• TPV at Pre-conversion Baseline

  TPV is the sum of the assessment in left and right distal common carotid arteries.

  Pre-conversion baseline

Secondary Outcomes (21)

• Annual Change Rate in Carotid Intima Media Thickness (CIMT) From Pre-conversion Baseline at 12, 18, 24 and 36 Months Post-transplant

  Pre-conversion baseline, and 12, 18, 24 and 36 months post-transplant

• CIMT at Pre-conversion Baseline

  Pre-conversion baseline

• Change From Pre-conversion Baseline in Carotid Plaque Roughness at 12 and 24 Months Post-transplant

  Pre-conversion baseline, 12, and 24 months post-transplant

• Change From Pre-conversion Baseline in Fasting Lipid Parameters at 12, 18, 24 and 36 Months Post-transplant

  Pre-conversion baseline, and 12, 18, 24 and 36 months post-transplant

• Change From Pre-conversion Baseline in Glucose at Months 12, 24 and 36 Post-transplant

  Pre-conversion baseline, 12, 24 and 36 months post-transplant

Study Arms (2)

1

ACTIVE COMPARATOR

Tacrolimus + MMF + Steroids

Drug: tacrolimus; Drug: mycophenolate mofetil; Drug: prednisone

2

EXPERIMENTAL

Tacrolimus + MMF + Steroids with conversion from Tacrolimus to Sirolimus at 3-4 months post-transplant

Drug: sirolimus; Drug: tacrolimus; Drug: mycophenolate mofetil; Drug: prednisone

Interventions

tacrolimus DRUG

The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol TAC should be initiated within 24 hours before or after transplantation or within 14 days of transplantation as per local standard of care and tapered to a target trough level of 3-10 ng/mL by the Pre-Conversion visit at month 3-4 post-transplantation. The target trough level of TAC will be maintained at 3-10 ng/mL through to the end of the study.

Also known as: CNI

1

mycophenolate mofetil DRUG

The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol MMF or MPS should be initiated within 24 hours before or after transplantation or within 14 days of transplantation per local standard of care and tapered to a minimum oral dose of MMF ≥ 500 mg/day or MPS ≥ 360 mg/day by the Pre-Conversion visit at month 3-4 post-transplantation. At the discretion of the investigator, MMF may be changed to MPS, or MPS may be changed to MMF. MMF is to be continued at ≥ 500 mg/day dose or MPS is to be continued at ≥ 360 mg/day dose through to the end of study.

Also known as: MMF, MPS

1

prednisone DRUG

The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol CCS should be initiated within 24 hours before or after transplantation or within 14 days of transplantation per local standard of care and tapered to a minimum of 5 mg/day of prednisone orally or the alternate day equivalent by the Pre-Conversion visit at month 3-4 post-transplant. Continue administration of prednisone as per local standard of care to a minimum dose of 2.5 mg/day or alternate day equivalent dose to the end of the study. Withdrawal of CCS is prohibited.

Also known as: CCS

1

sirolimus DRUG

The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol. On study Day 1 Conversion, the daily dose of TAC will not be taken, and SRL is initiated as a single 5-10 mg loading dose, followed by 3 mg/day on subsequent days, adjusted to maintain a SRL target trough level of 8-15 ng/mL through to month 24 post-transplant, then 5-12 ng/mL to the end of month 36 post-transplant.

2

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least one of the following characteristics:
• History of dialysis for at least 3 years.
• History of diabetes for at least 5 years.
• Hypertension or ischemic nephropathy as a cause of the end stage renal disease or loss of the first transplant.
• History of coronary artery disease, stroke, myocardial infarction, or amputation for vascular disease.

You may not qualify if:

• History of malignancy within the last 5 years (except adequately treated skin cancer).
• Recipients of non-renal organ transplant.
• Active gastrointestinal disease that may interfere with drug absorption.
• Active HIV, hepatitis B or C infection.
• Women who are pregnant or breastfeeding.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (8)

Pfizer Investigational Site

Rochester, New York, 14642, United States

Location

Pfizer Investigational Site

Calgary, Alberta, T2N 2T9, Canada

Location

Pfizer Investigational Site

Edmonton, Alberta, T6G 2B7, Canada

Location

Pfizer Investigational Site

Hamilton, Ontario, L8N 4A6, Canada

Location

Pfizer Investigational Site

London, Ontario, N6A 5A5, Canada

Location

Pfizer Investigational Site

Toronto, Ontario, M5B 1W8, Canada

Location

Pfizer Investigational Site

Toronto, Ontario, M5C 2T2, Canada

Location

Pfizer Investigational Site

Montreal, Quebec, H1T 2M4, Canada

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Atherosclerosis; Renal Insufficiency

Interventions

Tacrolimus; Mycophenolic Acid; Prednisone; Sirolimus

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2006
• First Posted: April 5, 2006
• Study Start: April 1, 2006
• Primary Completion: December 1, 2010
• Study Completion: January 1, 2012
• Last Updated: September 23, 2013
• Results First Posted: May 24, 2012

Record last verified: 2013-07

Locations

US (1); CA (7)