Study Evaluating The Use Of Sirolimus In Recipients Of Kidney Allografts From Expanded Criteria Donors (ECD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00697112
First received: June 10, 2008
Last updated: December 3, 2013
Last verified: December 2013
  Purpose

The purpose of this observational study is to examine the clinical outcomes of the use of sirolimus as base therapy in kidney allograft recipients from Expanded Criteria Donors (ECD) under conditions of routine clinical practice. The primary objective is to identify the current criteria/reasons to use sirolimus as base therapy in this selected population and define and understand the emerging patterns of immunosuppressive treatment with sirolimus.


Condition Intervention
Renal Transplantation
Drug: Sirolimus

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Surveillance Registry Of Sirolimus Use In Recipients Of Kidney Allograft From Expanded Criteria Donors (ECD)

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants With Main Reason for the Use of Sirolimus (Rapamune) Therapy [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The study employ a questionnaire which included different clinical criteria to determine the main medical reason for the introduction of sirolimus (Rapamune) therapy after renal transplant. The physician responsible selected the one that was considered the main reason for introduction of sirolimus (Rapamune) as base immunosuppressive therapy.


Secondary Outcome Measures:
  • Probability of Graft Survival [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    Graft survival was considered in participants who did not experience graft failure. Graft failure was determined by return to dialysis for a period of at least 12 weeks with no return of function, or graft loss whichever occurred sooner.

  • Probability of no Acute Rejection [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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: significant interstitial infiltration (greater than [>] 25 percent [%] of parenchyma affected) and foci of moderate tubulitis (5-10 cells/tubular cross section), Grade 1B: significant interstitial infiltration (>25% of parenchyma affected) and severe tubulitis (>10 mononuclear cells/tubular cross section), Grade 2A: mild-moderate intimal arteritis, Grade 2B: severe intimal arteritis comprising >25% of the luminal area and Grade 3: transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells. Probability of no acute rejection throughout the sirolimus (Rapamune) therapy was estimated using Kaplan-Meier method.

  • Probability of Participant Survival [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    Participant's survival defined as participant living with or without a functioning graft. Probability of participant survival throughout the sirolimus (Rapamune) therapy was estimated using Kaplan-Meier method.

  • Average Dose of Immunosuppressive Drugs Administered [ Time Frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 ] [ Designated as safety issue: No ]
    Immunosuppressive drugs administered included cyclosporin A (CsA) administration based on monitoring of plasma trough levels (C0), CsA administration based on monitoring of plasma levels 2-hours after CsA dose (C2), tacrolimus, and sirolimus (Rapamune).

  • Average Blood Level of Immunosuppressive Drugs Administered [ Time Frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 ] [ Designated as safety issue: No ]
    Immunosuppressive drugs administered included cyclosporin A (CsA) administration based on monitoring of plasma trough levels (C0), CsA administration based on monitoring of plasma levels 2-hours after CsA dose (C2), tacrolimus, and sirolimus (Rapamune).

  • Average Creatinine Clearance [ Time Frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 ] [ Designated as safety issue: No ]
    Creatinine clearance (CCr) is a measure of glomerular filtration rate (GMFR), an index 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 milliliter 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.

  • Average Proteinuria [ Time Frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 ] [ Designated as safety issue: No ]
    Proteinuria defined as the presence of an excess of serum proteins in the urine. Normal value of proteinuria is below 0.15 grams per 24 hours (g/24 hr).

  • Percentage of Participants Who Prematurely Discontinued the Sirolimus (Rapamune) Therapy [ Time Frame: Baseline up to Month 12 ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Prematurely Discontinued the Sirolimus (Rapamune) Therapy Due to Inefficacy [ Time Frame: Baseline up to Month 12 ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Prematurely Discontinued the Sirolimus (Rapamune) Therapy Due to Adverse Events [ Time Frame: Baseline up to Month 12 ] [ Designated as safety issue: Yes ]
    An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Participants who discontinued sirolimus (Rapamune) therapy prematurely due to AE were obliged to discontinue sirolimus (Rapamune) therapy permanently, are reported.

  • Body Mass Index [ Time Frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 ] [ Designated as safety issue: Yes ]
    BMI was calculated as weight divided by height squared and measured as kilogram per square meter (kg/m^2).

  • Number of Participants With Body Temperature [ Time Frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 ] [ Designated as safety issue: Yes ]
    Body temperature was measured in degree Celsius. Each participants were classified into three different categories based on their body temperature: body temperature less than 35 degree Celsius = hypothermia, body temperature between 35 to 37.5 degree Celsius = feverless, and body temperature greater than 37.5 degree Celsius = fever.

  • Blood Pressure [ Time Frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 ] [ Designated as safety issue: Yes ]
    Systolic and diastolic blood pressure (BP) was measured after the participant had rested in the supine position for at least 5 minutes with the participant's arm supported at the level of the heart, and recorded to the nearest millimeters of mercury (mmHg).

  • Pulse Rate [ Time Frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 ] [ Designated as safety issue: Yes ]
  • Body Weight [ Time Frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 ] [ Designated as safety issue: Yes ]
  • Percentage of Participants With Physical Abnormalities [ Time Frame: Baseline up to Month 12 ] [ Designated as safety issue: Yes ]
    Physical abnormalities included all the abnormalities related to general disorders and administration site conditions, gastrointestinal disorders, skin and subcutaneous tissue disorders, vascular disorders, investigations, infections and infestations, eye disorders, respiratory, thoracic and mediastinal disorders, nervous system disorders, musculoskeletal and connective tissue disorders, injury, poisoning and procedural complications, surgical and medical procedures, psychiatric disorders, neoplasms benign, malignant and unspecified (incl cysts and polyps), ear and labyrinth disorders, and congenital, familial and genetic disorders.

  • Percentage of Participants With Adverse Events [ Time Frame: Baseline up to Month 12 ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug.

  • Percentage of Participants With Serious Adverse Events [ Time Frame: Baseline up to Month 12 ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  • Percentage of Participants With Clinically-Significant Electrocardiogram Abnormalities [ Time Frame: Baseline up to Month 12 ] [ Designated as safety issue: Yes ]
    Standard 12-lead ECG was performed. ECG intervals included PR interval (time between the onset of atrial depolarization and the onset of ventricular depolarization), QRS interval (represented ventricular depolarization), QT interval (time corresponding to the beginning of depolarization to repolarization of the ventricles) corrected using Fridericia's formula (QTcF = QT divided by cube root of RR interval) and heart rate (time interval between consecutive heart beats [RR interval]).

  • Percentage of Participants With Clinically-Significant Radiological Abnormalities [ Time Frame: Baseline up to Month 12 ] [ Designated as safety issue: Yes ]
    Radiological examination was performed to evaluate presence or signs of infections or pneumonitis.


Enrollment: 53
Study Start Date: May 2008
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
A Drug: Sirolimus
Non interventional. Sirolimus administered by Principal Investigator per standard practice and labeling.
Other Name: Rapamune

Detailed Description:

pilot study

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Kidney allograft recipients

Criteria

Inclusion Criteria:

  • Patients aged 18 years or older.
  • Patients who received a renal transplant (primary, secondary, tertiary, etc.) without pancreas, from Expanded Criteria Donors (ECD), 3 months prior and no later than 1 year at the time of study enrollment.
  • Patients who provided informed consent.
  • Patients without sirolimus as base therapy.

Exclusion Criteria:

  • Patients who are unwilling or unable to provide informed consent or who lack a legal guardian or designee able to provide consent on their behalf.
  • Patients who are unable to complete the study.
  • Patients who are participating in another clinical trial during the last 6 months.
  • Pregnant or lactating patients.
  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: NCT00697112

Locations
Argentina
Pfizer Investigational Site
Caba, Buenos Aires, Argentina, 1425
Pfizer Investigational Site
Caba, Buenos Aires, Argentina, C1181ACH
Pfizer Investigational Site
Caba, Buenos Aires, Argentina
Pfizer Investigational Site
Caba, Buenos Aires, Argentina, C1093AAS
Pfizer Investigational Site
Barrio General Paz, Cordoba, Argentina, 5016
Pfizer Investigational Site
Cordoba, Argentina, 5016
Pfizer Investigational Site
Santa Fe, Argentina, 3000
Pfizer Investigational Site
Tucuman, Argentina, 4000
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00697112     History of Changes
Other Study ID Numbers: 0468H-102385, B1741025
Study First Received: June 10, 2008
Results First Received: December 3, 2013
Last Updated: December 3, 2013
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Additional relevant MeSH terms:
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 20, 2014