Prednisone Withdrawal Versus Prednisone Maintenance After Kidney Transplant

This study has been terminated.
(due to low study enrollment)
Sponsor:
Information provided by:
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00596947
First received: January 8, 2008
Last updated: February 18, 2011
Last verified: February 2011
  Purpose

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).


Condition Intervention Phase
Transplants and Implants
Drug: prednisone
Drug: rabbit antithymocyte globulin
Drug: Tacrolimus
Drug: Prednisone
Drug: Mycophenolate mofetil
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized, Prospective Single-center Study Comparing a Rapid Discontinuation of Corticosteroids (Steroid Withdrawal) With Corticosteroid Therapy in Kidney Transplantation Using Mycophenolate Mofetil and Tacrolimus Maintenance Therapy

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • The Number of Participants With Acute Rejection Episodes [ Time Frame: 6 and 12 months post-transplant ] [ Designated as safety issue: No ]
    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.

  • The Number of Participants With Graft Survival [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
    The number of participants who did not experience graft failure (defined as return to dialysis) at 6 and 12 months would have been reported.

  • Participant Survival [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
    The number of participants alive at 6 and 12 months post-transplant would have been posted as a measure of patient survival.


Secondary Outcome Measures:
  • The Number of Participants With Treatment Failures [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    This measure was defined as the percentage of participants that did not remain on initial therapy (ie were withdrawn from each arm of the trial)

  • Length of Hospital Stay After Transplant [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    The length of the hospital stay would have assessed the number of days a participant was in the hospital after the kidney transplant was performed. This is calculated from date of admission to date of discharge.

  • The Number of Participants With Hospital Readmissions [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    The number of readmissions during the study period for each participant would have been assessed, as well as the reason for readmissions.

  • The Length of Stay Associated With Hospital Readmissions [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    The time from admission to discharge for each readmission for patients readmitted in the first 12 months post-transplant.

  • Participant Renal Function as Measured by MDRD Formula [ Time Frame: 3, 6 and 12 months ] [ Designated as safety issue: Yes ]
    The above methods focus on estimating or determining actual glomerular filtration rate (GFR) (or renal function) of the kidney transplant. The MDRD (Modification of Diet in Renal Disease) calculation includes age, sex and serum creatinine would have provided an estimate of GFR. This was to be performed at 3,6 and 12 months post-transplant.

  • Participant Renal Function as Measured by 24 Hour Urine Collection [ Time Frame: 3 and 12 months post-transplant ] [ Designated as safety issue: Yes ]
    Results would have been reported from patients undergoing 24 hour urine collections at 3 and 12 months post-transplant. This is a way to measure glomerular function rate (GFR) or renal function.

  • The Number of Participants With the Need for Rabbit Antithymocyte Globulin to Treat Rejection Episodes. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    The incidence and severity of rejection episodes per participant would have been identified by kidney transplant biopsy results read by a transplant pathologist. Treatment of rejection episodes in each participant would have been determined by the treating transplant physician.

  • The Number of Participants With Leukopenia [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    All participants would have been assessed for the presence at any time during the trial of: leukopenia (defined by lab results as a white count less than 3,000 cells/uL).

  • The Number of Participants With Infections [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Participants would have been monitored throughout the study for any infectious complications as confirmed by the principal investigator. Patients would have been monitored by urine cytology and blood polymerase chain reaction for BK virus at baseline, and months 3, 6 and 12 post-transplant.

  • The Number of Participants With Malignancy [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Participants would have been monitored throughout the study with any reports of malignancy being confirmed by principal investigator.

  • The Number of Participants With Hypertension [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    The number of participants who developed hypertension defined as blood pressure greater than 140/90 throughout the first 12 months of the study.

  • The Number of Participants With Hyperlipidemia [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Fasting lipid profiles were to be performed at 3,6 and 12 months post-transplant. Definitions based on ATP III guidelines.

  • The Number of Participants With Bone Disease [ Time Frame: baseline (within 1 month post-transplant), 3, 6, 12 and 24 months ] [ Designated as safety issue: Yes ]
    Bone densitometry by Computed tomography of peripheral skeleton and DEXA scans were performed at baseline (within one month after transplant) Urine and blood samples to measure markers of bone turnover: Alkaline phosphatase, pyridinoline, serum 1-25 vit D 3 levels (calcitriol) and 25 hydroxy vit D (calcidiol) levels and serum osteocalcin levels were drawn at baseline, 3, 6, 12 and 24 months.

  • The Number of Participants With Post Transplant Diabetes Mellitus [ Time Frame: pre-transplant in living donor recipients, baseline (within one month post-transplant) and at 3, 6 and 12 months ] [ Designated as safety issue: Yes ]

    Glucose tolerance test performed in non-diabetic participants only at pre transplant in living donor recipients and at baseline (within 1 mo after transplant) and 6 mo and 12 months. Blood test for hemoglobin A1C in non diabetic participants only: at baseline, 3, 6, and 12 months.

    Insulin and C peptide levels at baseline, 3,6 and 12 months in all participants.


  • The Number of Participants With Weight Gain [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Height, weight will be used to calculate change in BMI for all participants.


Enrollment: 18
Study Start Date: October 2005
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prednisone Withdrawal
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
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.
Other Names:
  • Deltasone
  • Steroids
  • Prednisone
  • Methylprednisolone
  • Corticosteroids
Drug: rabbit antithymocyte globulin
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.
Other Names:
  • RATG
  • Thymoglobulin
  • Rabbit antithymocyte globulin
  • Polyclonal antibody
Drug: Tacrolimus
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.
Other Names:
  • Prograf
  • Tacrolimus
Drug: Mycophenolate mofetil
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.
Other Names:
  • mmf
  • CellCept
Active Comparator: Prednisone Maintenance
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
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.
Other Names:
  • RATG
  • Thymoglobulin
  • Rabbit antithymocyte globulin
  • Polyclonal antibody
Drug: Tacrolimus
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.
Other Names:
  • Prograf
  • Tacrolimus
Drug: Prednisone
Participants in this group continued on prednisone indefinitely. Participants began with 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, 20 mg days 5-9, 15 mg day 10-19, 10 mg day 20-24, 7.5 mg day 25-29, and 5mg from day 30-on indefinitely.
Other Names:
  • Deltasone
  • Steroids
  • Prednisone
  • Methylprednisolone
  • Corticosteroids
Drug: Mycophenolate mofetil
Participants in both groups received mycophenolate mofetil by mouth twice daily indefinitely. Dosing for patients in the Prednisone maintenance group was 500 mg 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.
Other Names:
  • mmf
  • CellCept

Detailed Description:

Corticosteroids (one specific type is prednisone) have been used in clinical transplantation for more than 30 years. There are many side effects of corticosteroids including significant bone disease, diabetes (elevated blood sugar levels), fluid retention and hypertension (high blood pressure), psychosis, peptic ulcer disease, hyperlipidemia (elevated lipid levels such as cholesterol and triglycerides), obesity (overweight), acne, and susceptibility to infections. It is hoped that the new generation of potent immunosuppressive medications (such as Prograf and CellCept) will permit avoidance or withdrawal of corticosteroids for the majority of patients to avoid both short- and long-term complications of corticosteroid use in kidney transplant recipients.

  Eligibility

Ages Eligible for Study:   19 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00596947

Locations
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Simin Goral, MD University of Pennsylvania-Renal Electrolyte and Hypertension Division
  More Information

No publications provided

Responsible Party: Simin Goral, Hospital of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00596947     History of Changes
Other Study ID Numbers: 803242
Study First Received: January 8, 2008
Results First Received: February 18, 2011
Last Updated: February 18, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pennsylvania:
kidney transplantation
tacrolimus
Prograf
mycophenolate mofetil
CellCept
corticosteroid withdrawal
prednisone withdrawal
prednisone maintenance
rabbit antithymocyte globulin
Thymoglobulin

Additional relevant MeSH terms:
Antilymphocyte Serum
Mycophenolate mofetil
Tacrolimus
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisone
Prednisolone hemisuccinate
Prednisolone phosphate
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 28, 2014