Prednisone Withdrawal Versus Prednisone Maintenance After Kidney Transplant

NCT00596947 | Terminated Phase 4 Results

• 1 other identifier: 803242
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study was to determine if rapid discontinuation of corticosteroids (also known as prednisone withdrawal) and maintenance immunosuppression with Prograf (tacrolimus) and CellCept (mycophenolate mofetil) while using Thymoglobulin (Rabbit antithymocyte globulin) will give similar safety and efficacy results compared to continuation of corticosteroids (also known as prednisone maintenance) and standard maintenance immunosuppression with Prograf (tacrolimus), CellCept (mycophenolate mofetil) while using Thymoglobulin (Rabbit antithymocyte globulin).

Conditions

Transplants and Implants

Keywords

kidney transplantation; tacrolimus; Prograf; mycophenolate mofetil; CellCept; corticosteroid withdrawal; prednisone withdrawal; prednisone maintenance; rabbit antithymocyte globulin; Thymoglobulin

Outcome Measures

Primary Outcomes (3)

• The Number of Participants With Acute Rejection Episodes

  Acute rejection episodes would have been measured by the number of participants who underwent a kidney transplant biopsy, and had the results of the biopsy reported as acute rejection by the transplant pathologist. Biopsies were only performed if clinically indicated. The cumulative number of participants with recorded rejection episodes by 6 and 12 months post-transplant would have been reported.

  6 and 12 months post-transplant

• The Number of Participants With Graft Survival

  The number of participants who did not experience graft failure (defined as return to dialysis) at 6 and 12 months would have been reported.

  6 and 12 months

• Participant Survival

  The number of participants alive at 6 and 12 months post-transplant would have been posted as a measure of patient survival.

  6 and 12 months

Secondary Outcomes (15)

• The Number of Participants With Treatment Failures

  12 months

• Length of Hospital Stay After Transplant

  12 months

• The Number of Participants With Hospital Readmissions

  12 months

• The Length of Stay Associated With Hospital Readmissions

  12 months

• Participant Renal Function as Measured by MDRD Formula

  3, 6 and 12 months

Study Arms (2)

Prednisone Withdrawal

EXPERIMENTAL

Participants randomized to the prednisone withdrawal group, received 4 medications to prevent rejection. Thymoglobulin (rabbit antithymocyte globulin) was given intravenously in the operating room at the time of transplant. Subsequent intravenous doses were administered to participants an inpatient or outpatient for a total of 3 to 5 doses. Participants also began taking Prograf (tacrolimus) and CellCept (mycophenolate mofetil)orally within 24 hours of transplant and continued indefinitely. The steroids were initially given in the operating room intravenously at time of transplant as Solu-medrol (methylprednisolone)and were then switched to daily oral prednisone doses. The participant's dose of prednisone was rapidly decreased until it was completely eliminated by day 6 post-transplant.

Drug: prednisone; Drug: rabbit antithymocyte globulin; Drug: Tacrolimus; Drug: Mycophenolate mofetil

Prednisone Maintenance

ACTIVE COMPARATOR

Participants randomized to the prednisone maintenance group, received 4 medications to prevent rejection. Thymoglobulin (rabbit antithymocyte globulin) was initiated intravenously in the operating room at the time of transplant. Subsequent intravenous doses were administered an inpatient or outpatient for a total of 3 to 5 doses. Participants began taking Prograf (tacrolimus) and CellCept (mycophenolate mofetil)orally within 24 hours of transplant and continued on them indefinitely. The steroids were initially given intravenously in the operating room at time of transplant as Solu-medrol (methylprednisolone) and were then switched to daily oral prednisone tablets. Participants remained on all drugs according to their doctor's standard of care, and the prednisone was not be eliminated.

Drug: rabbit antithymocyte globulin; Drug: Tacrolimus; Drug: Prednisone; Drug: Mycophenolate mofetil

Interventions

Prednisone DRUG

In this group, participants had prednisone rapidly decreased until completely eliminated by day 6 after transplant. Participants began on 500mg of intravenous methylprednisolone on the day of transplant, followed by the following doses of oral prednisone: 160mg on day 1, 120mg on day 2, 80mg on day 3, 40mg on day 4, 20mg on day 5, none from day 6-on.

Also known as: Deltasone, Steroids, Methylprednisolone, Corticosteroids

Prednisone Withdrawal

rabbit antithymocyte globulin DRUG

Participants in both groups received 3 to 5 doses of an intravenous medication to prevent rejection called Thymoglobulin (rabbit antithymocyte globulin) as per our standard of care. This drug was dosed at 1.5 milligrams/killograms per dose and dosing was then based on body weight. The dose was decreased in half or held if the participant had a low white blood cell count or if the participant a low platelet count. The first dose was given intravenously in the operating room and subsequent intravenous doses were administered either while participants were inpatients or outpatients for a total of 3 to 5 doses for a total of up to 6mg/kg. The number of doses was based on transplant kidney function and risk factors for rejection.

Also known as: RATG, Thymoglobulin, Polyclonal antibody

Prednisone Maintenance; Prednisone Withdrawal

Tacrolimus DRUG

Participants in both groups received tacrolimus per our standard of care. This medication helped to prevent rejection and was initially dosed at 0.1-0.2 milligrams/killograms/day in two divided doses, given orally, based on participant's body weight. We then looked at the trough levels of this medication(the lowest level before the next dose), and aimed to keep the trough level between 5-10 nanograms/milliliter throughout the study.

Also known as: Prograf

Prednisone Maintenance; Prednisone Withdrawal

Mycophenolate mofetil DRUG

Participants in both groups received mycophenolate mofetil by mouth twice daily indefinitely. Dosing for patients in the Prednisone withdrawal group was 1000mg orally twice daily. The dose was decreased or held at the discretion of the physician, for side effects such as low white blood cell count, or low platelet count, or if the participant experienced stomach side effects such as heartburn, nausea, vomiting or diarrhea.

Also known as: mmf, CellCept

Prednisone Withdrawal

Eligibility Criteria

• Age: 19 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• First time kidney transplant recipients who receives a kidney from a cadaveric, living related or living unrelated donor
• Age greater than 18 years and less than 75 years
• Caucasian recipients
• Patients with current low panel reactive antibody (PRA) levels (\<10%)
• Patients with signed and dated informed consent
• Women of childbearing potential must have a negative pregnancy test at baseline and agree to use a medically acceptable method of contraception throughout the treatment period.

You may not qualify if:

• Other than Caucasian ethnicity
• Patients with HIV+ or
• Patients with HbsAg+ or Hepatitis C positive
• Patients with a history of malignancy in the past 5 years
• Patients with active systemic or localized major infection
• Patients with a history of chronic steroid use for other diseases

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Interventions

Prednisone; Steroids; Methylprednisolone; Adrenal Cortex Hormones; thymoglobulin; Tacrolimus; Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds; Prednisolone; Pregnadienetriols; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Limitations and Caveats

The trial was terminated early due to low enrollment. Therefore no results beyond basic results section are reported due to uninterpretable data.

Results Point of Contact

• Title: Jennifer Trofe-Clark, Clinical Transplant Research Pharmacist
• Organization: Hospital of the University of Pennsylvania

jennifer.trofe-clark@uphs.upenn.edu

215-614-4274

Study Officials

• Simin Goral, MD

  University of Pennsylvania-Renal Electrolyte and Hypertension Division

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Polycystic Kidney Disease Clinic

Study Record Dates

• First Submitted: January 8, 2008
• First Posted: January 17, 2008
• Study Start: October 1, 2005
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: May 15, 2017
• Results First Posted: March 21, 2011

Record last verified: 2017-03

Locations

US (1)