Back to resultsOpen Label Comparative Study Of De Novo Renal Allograft Recipients Receiving CSA + MMF + Corticosteroids Versus CSA + Rapamune + Corticosteroids
Primary Purpose
Inflammation
Status
Completed
Phase
Phase 4
Locations
Iran, Islamic Republic of
Study Type
Interventional
Intervention
CsA+Rapamune+CS
CsA+MMF+CS
Sponsored by
About this trial
This is an interventional treatment trial for Inflammation
Eligibility Criteria
Inclusion Criteria:
- Age 13 years and weight 40 kg
- End-stage renal disease, with patients receiving a primary or secondary renal allograft from a living-unrelated donor, or from a living-related donor.
- Women who are of childbearing potential must have a negative pregnancy test before enrollment in the study and agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months following discontinuation from the study.
- Total white blood cell count 4.0 x 109/L (4,000/mmP3P), platelet count 100 x 10P9P/L(100,000/mmP3P), fasting triglycerides ≤ 4.6 mmol/L (400 mg/dL), fasting cholesterol ≤ 7.8 mmol/L (300 mg/dL). If it is not possible to obtain fasting triglycerides and cholesterol before surgery, historical values (within 1 year) may be used.
- Signed and dated informed consent (parent or legal guardian must provide consent for patients <18 years of age). An assent form will be signed by patients < 18 years of age enrolled in the study.
Exclusion Criteria:
- Evidence of active systemic or localized major infection at the time of initial Sirolimus administration.
- Cadaveric donors
- History of malignancy within 5 years before enrollment into the study (with the exception of adequately treated basal cell or squamous cell carcinoma of the skin)
- Use of any investigational drug other than specified in the protocol during the 4 weeks before enrolling in the study.
- Use of planned antibody induction therapy at the time of transplantation.
- Active gastrointestinal disorder that may interfere with drug absorption.
- Known hypersensitivity to Sirolimus, MMF or Cyclosporine or its derivatives.
- Multiple organ transplants (2 or more organ transplant e.g. Kidney and Pancreas).
- Patient with high risk of rejection (eg. Patients with a PRA >50%, black patients and patients with 2nd transplant who lost their first graft within the first 6 months).
- Evidence of infiltrate, cavitation, or consolidation on chest x-ray obtained during pre-study screening
Sites / Locations
- Labbafinejad Hospital
- Modarres Hospital
- Shariati Hospital
- Taleqani Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Arm A (CsA+Rapamune+CS)
Arm B (CsA+MMF+CS)
Arm Description
Outcomes
Primary Outcome Measures
Incidence of Efficacy Failure
Efficacy failure was defined as first occurrence of either biopsy confirmed acute rejection, graft loss or death within 12 months of post-transplantation. Percentage of participants with efficacy failure was reported.
Secondary Outcome Measures
Serum Creatinine Level
Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. An increased level of creatinine in the blood indicates decreased kidney function. Normal adult blood levels of creatinine are 0.5 to 1.1 milligram per deciliter (mg/dL) for females and 0.6 to 1.2 mg/dL for males; however, the normal values are age-dependent as elderly patients typically have smaller muscle mass.
Creatinine Clearance
Creatinine clearance (CCr) is a measure of kidney function. CCr is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 millimeters per minute (mL/min) and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function.
Glomerular Filtration Rate (GFR) by Nankivell Method
GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR was calculated using the Nankivell formula. GFR by Nankivell equation= (6.7 per serum creatinine) plus (0.25*body weight) minus (0.5*serum urea) minus (100 per height square) plus (35 for male or 25 for female). A normal GFR is greater than (>)90 mL/min per 1.73 m^2 [mL/min/1.73 m^2], although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR less than (<)15 mL/min/1.73 m^2 indicated kidney failure.
Incidence of Biopsy-Confirmed Acute Rejection
Diagnosis of acute rejection was made via kidney biopsy using Banff criteria. Percentage of participants with biopsy-confirmed acute rejection was reported.
Histologic Grade of First Acute Rejection
Diagnosis of acute rejection was made via kidney biopsy. Categorization of biopsies with suspected acute rejection was based on histological findings using updated 1997 Banff criteria. Grade 1A: cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (5-10 cells/tubular cross section), Grade 1B: with severe tubulitis (>10 cells/tubular cross section), Grade 2A: mild-moderate intimal arteritis, Grade 2B: severe intimal arteritis and Grade 3: transmural arterits and/or fibrinoid necrosis. Data is reported as percentage of participants.
Percentage of Participants Who Survived
Survival defined as participants living with or without a functioning graft.
Percentage of Participants With Graft Survival
Graft survival defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.
Incidence of Presumptive or Documented Infection
Presumptive or documented infection during the 12 months after transplantation; was confirmed by culture, biopsy, or serology and reported. Percentage of participants with presumptive or documented infection was reported.
Incidence of Histologically Confirmed Lymphoproliferative Disease
Lymphoproliferative disorder represents an abnormal proliferation of B cells in response to either primary or reactivated infection with Epstein-Barr virus. Percentage of participants with histologically confirmed lymphoproliferative disease was reported.
Percentage of Participants With Efficacy Failure or Premature Elimination
Efficacy failure was defined as the first occurrence of acute rejection, graft loss, or death. Premature elimination was defined as elimination from the study for any other reason.
Incidence of Anemia
Diagnostic criterion for anemia was based on the laboratory results; in men: hemoglobin (Hb) <14 gram per deciliter (g/dL), hematocrit (Hct) <42%, or red blood cells (RBCs) <4.5 million/liter (million/L); for women: Hb <12 g/dL, Hct <37%, or RBC < 4 million/L. Percentage of participants with anaemia was reported.
Number of Participants Who Discontinued
Number of participants who discontinued the study treatment due to any reason is reported.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01601821
Brief Title
Open Label Comparative Study Of De Novo Renal Allograft Recipients Receiving CSA + MMF + Corticosteroids Versus CSA + Rapamune + Corticosteroids
Official Title
An Open Label Comparative Study Of De Novo Renal Allograft Recipients Receiving CSA + MMF + Corticosteroids Versus CSA + Rapamune + Corticosteroids With Further CSA Elimination In The Rapamune Arm With The Introduction Of MMF
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
April 2006 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
March 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
To compare the safety and efficacy of cyclosporine (CsA) + mycophenolate mofetil (MMF) + corticosteroids © to CsA + Rapamune + Cs with CsA elimination in the Rapamune arm with the introduction of MMF in de novo renal allograft recipients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
245 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A (CsA+Rapamune+CS)
Arm Type
Active Comparator
Arm Title
Arm B (CsA+MMF+CS)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
CsA+Rapamune+CS
Intervention Description
Part 1: Rapamune will be given as a loading dose of 6 mg once followed by maintenance dose of 2 mg to achieve a target trough level of 8-15 ng/ml. Part 2: Rapamune dose will be adjusted to achieve a target trough level of 10-15ng/ml through 6 months
Intervention Type
Drug
Intervention Name(s)
CsA+MMF+CS
Intervention Description
The control arm is the standard local practice (official protocol) in Iran:
Cyclosporine + MMF + Corticosteroid. The time period is from pre-study screening / baseline evaluation up to 12 months for patients who are maintained on CsA + MMF + CS.
Primary Outcome Measure Information:
Title
Incidence of Efficacy Failure
Description
Efficacy failure was defined as first occurrence of either biopsy confirmed acute rejection, graft loss or death within 12 months of post-transplantation. Percentage of participants with efficacy failure was reported.
Time Frame
Baseline up to Month 12
Secondary Outcome Measure Information:
Title
Serum Creatinine Level
Description
Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. An increased level of creatinine in the blood indicates decreased kidney function. Normal adult blood levels of creatinine are 0.5 to 1.1 milligram per deciliter (mg/dL) for females and 0.6 to 1.2 mg/dL for males; however, the normal values are age-dependent as elderly patients typically have smaller muscle mass.
Time Frame
Month 3, 6, 12
Title
Creatinine Clearance
Description
Creatinine clearance (CCr) is a measure of kidney function. CCr is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 millimeters per minute (mL/min) and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function.
Time Frame
Month 3, 6, 12
Title
Glomerular Filtration Rate (GFR) by Nankivell Method
Description
GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR was calculated using the Nankivell formula. GFR by Nankivell equation= (6.7 per serum creatinine) plus (0.25*body weight) minus (0.5*serum urea) minus (100 per height square) plus (35 for male or 25 for female). A normal GFR is greater than (>)90 mL/min per 1.73 m^2 [mL/min/1.73 m^2], although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR less than (<)15 mL/min/1.73 m^2 indicated kidney failure.
Time Frame
Month 3, 6, 12
Title
Incidence of Biopsy-Confirmed Acute Rejection
Description
Diagnosis of acute rejection was made via kidney biopsy using Banff criteria. Percentage of participants with biopsy-confirmed acute rejection was reported.
Time Frame
Baseline up to Month 6
Title
Histologic Grade of First Acute Rejection
Description
Diagnosis of acute rejection was made via kidney biopsy. Categorization of biopsies with suspected acute rejection was based on histological findings using updated 1997 Banff criteria. Grade 1A: cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (5-10 cells/tubular cross section), Grade 1B: with severe tubulitis (>10 cells/tubular cross section), Grade 2A: mild-moderate intimal arteritis, Grade 2B: severe intimal arteritis and Grade 3: transmural arterits and/or fibrinoid necrosis. Data is reported as percentage of participants.
Time Frame
Baseline up to Month 12
Title
Percentage of Participants Who Survived
Description
Survival defined as participants living with or without a functioning graft.
Time Frame
Month 12
Title
Percentage of Participants With Graft Survival
Description
Graft survival defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.
Time Frame
Month 12
Title
Incidence of Presumptive or Documented Infection
Description
Presumptive or documented infection during the 12 months after transplantation; was confirmed by culture, biopsy, or serology and reported. Percentage of participants with presumptive or documented infection was reported.
Time Frame
Baseline up to Month 12
Title
Incidence of Histologically Confirmed Lymphoproliferative Disease
Description
Lymphoproliferative disorder represents an abnormal proliferation of B cells in response to either primary or reactivated infection with Epstein-Barr virus. Percentage of participants with histologically confirmed lymphoproliferative disease was reported.
Time Frame
Baseline up to Month 12
Title
Percentage of Participants With Efficacy Failure or Premature Elimination
Description
Efficacy failure was defined as the first occurrence of acute rejection, graft loss, or death. Premature elimination was defined as elimination from the study for any other reason.
Time Frame
Month 12
Title
Incidence of Anemia
Description
Diagnostic criterion for anemia was based on the laboratory results; in men: hemoglobin (Hb) <14 gram per deciliter (g/dL), hematocrit (Hct) <42%, or red blood cells (RBCs) <4.5 million/liter (million/L); for women: Hb <12 g/dL, Hct <37%, or RBC < 4 million/L. Percentage of participants with anaemia was reported.
Time Frame
Baseline up to Month 12
Title
Number of Participants Who Discontinued
Description
Number of participants who discontinued the study treatment due to any reason is reported.
Time Frame
Month 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 13 years and weight 40 kg
End-stage renal disease, with patients receiving a primary or secondary renal allograft from a living-unrelated donor, or from a living-related donor.
Women who are of childbearing potential must have a negative pregnancy test before enrollment in the study and agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months following discontinuation from the study.
Total white blood cell count 4.0 x 109/L (4,000/mmP3P), platelet count 100 x 10P9P/L(100,000/mmP3P), fasting triglycerides ≤ 4.6 mmol/L (400 mg/dL), fasting cholesterol ≤ 7.8 mmol/L (300 mg/dL). If it is not possible to obtain fasting triglycerides and cholesterol before surgery, historical values (within 1 year) may be used.
Signed and dated informed consent (parent or legal guardian must provide consent for patients <18 years of age). An assent form will be signed by patients < 18 years of age enrolled in the study.
Exclusion Criteria:
Evidence of active systemic or localized major infection at the time of initial Sirolimus administration.
Cadaveric donors
History of malignancy within 5 years before enrollment into the study (with the exception of adequately treated basal cell or squamous cell carcinoma of the skin)
Use of any investigational drug other than specified in the protocol during the 4 weeks before enrolling in the study.
Use of planned antibody induction therapy at the time of transplantation.
Active gastrointestinal disorder that may interfere with drug absorption.
Known hypersensitivity to Sirolimus, MMF or Cyclosporine or its derivatives.
Multiple organ transplants (2 or more organ transplant e.g. Kidney and Pancreas).
Patient with high risk of rejection (eg. Patients with a PRA >50%, black patients and patients with 2nd transplant who lost their first graft within the first 6 months).
Evidence of infiltrate, cavitation, or consolidation on chest x-ray obtained during pre-study screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Labbafinejad Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Modarres Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Shariati Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Taleqani Hospital
City
Tehran
Country
Iran, Islamic Republic of
12. IPD Sharing Statement
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=0468H-102012
Description
To obtain contact information for a study center near you, click here.
Learn more about this trial
Open Label Comparative Study Of De Novo Renal Allograft Recipients Receiving CSA + MMF + Corticosteroids Versus CSA + Rapamune + Corticosteroids
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