Prednisone Withdrawal Versus Prednisone Maintenance After Kidney Transplant - Full Text View

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 Intervention Model: Parallel Assignment Masking: No masking 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:

MedlinePlus related topics: Kidney Transplantation Steroids

Drug Information available for: Prednisone Tacrolimus Mycophenolate mofetil

U.S. FDA Resources

Further study details as provided by Simin Goral, University of Pennsylvania:

Primary Outcome Measures:

The Number of Participants With Acute Rejection Episodes [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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:

The Number of Participants With Treatment Failures [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Hypertension [ Time Frame: 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 [ Time Frame: 12 months ]
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 ]
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 ]
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 ]
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 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 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 Name: Prograf 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 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 Name: Prograf 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 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

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
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
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 Name: Prograf

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
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 Name: Prograf

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
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 (Adult, Senior)
Sexes Eligible for Study:	All
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


Responsible Party:	Simin Goral, Director, Polycystic Kidney Disease Clinic, 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:	March 29, 2017

Keywords provided by Simin Goral, University of Pennsylvania:


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

Additional relevant MeSH terms:


Prednisolone acetate Methylprednisolone acetate Prednisone Methylprednisolone Methylprednisolone Hemisuccinate Prednisolone Prednisolone hemisuccinate Prednisolone phosphate Mycophenolic Acid Tacrolimus Mycophenolate mofetil Antilymphocyte Serum Anti-Inflammatory Agents Glucocorticoids Hormones	Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Calcineurin Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antibiotics, Antineoplastic Antiemetics Autonomic Agents Peripheral Nervous System Agents Gastrointestinal Agents Neuroprotective Agents

Prednisolone acetate
Methylprednisolone acetate
Prednisone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Mycophenolic Acid
Tacrolimus
Mycophenolate mofetil
Antilymphocyte Serum
Anti-Inflammatory Agents
Glucocorticoids
Hormones

Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents

ClinicalTrials.gov processed this record on June 23, 2017