Prednisone Withdrawal Versus Prednisone Maintenance After Kidney Transplant

Phase 4

Terminated

Conditions: Transplants and Implants

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

Registration Number: NCT00596947

Lead Sponsor: University of Pennsylvania

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).

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 18

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prednisone Withdrawal	Prednisone	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.
Prednisone Withdrawal	rabbit antithymocyte globulin	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.
Prednisone Withdrawal	Tacrolimus	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.
Prednisone Withdrawal	Mycophenolate mofetil	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.
Prednisone Maintenance	rabbit antithymocyte globulin	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.
Prednisone Maintenance	Tacrolimus	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.
Prednisone Maintenance	Prednisone	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.
Prednisone Maintenance	Mycophenolate mofetil	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.

Primary Outcome Measures

Name	Time	Method
The Number of Participants With Acute Rejection Episodes	6 and 12 months post-transplant	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	6 and 12 months	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	6 and 12 months	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

Name	Time	Method
The Number of Participants With Treatment Failures	12 months	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	12 months	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	12 months	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	12 months	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	3, 6 and 12 months	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	3 and 12 months post-transplant	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.	12 months	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	12 months	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	12 months	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	12 months	Participants would have been monitored throughout the study with any reports of malignancy being confirmed by principal investigator.
The Number of Participants With Bone Disease	baseline (within 1 month post-transplant), 3, 6, 12 and 24 months	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	pre-transplant in living donor recipients, baseline (within one month post-transplant) and at 3, 6 and 12 months	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	12 months	Height, weight will be used to calculate change in BMI for all participants.
The Number of Participants With Hypertension	12 months	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	12 months	Fasting lipid profiles were to be performed at 3,6 and 12 months post-transplant. Definitions based on ATP III guidelines.