Sirolimus Therapy for Poor Prognosis Immunoglobulin A Nephropathy (SIREPNA)

This study has been completed.
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Josep m Cruzado, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier:
NCT00396721
First received: November 3, 2006
Last updated: September 14, 2011
Last verified: September 2011
  Purpose

The purpose of this study is to test in a pilot trial the efficacy and tolerance of sirolimus oral (at low doses) in patient to treat poor-prognosis IgA Nephropathy.


Condition Intervention Phase
Glomerulonephritis, IGA
Nephropathy, IGA
IGA Nephropathy
Drug: ACE inhibitor + statin
Drug: Sirolimus (study drug)+ACE inhibitor + statin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Trial of Treatment of Poor-Prognosis IgA Nephropathy With Low Exposure to Sirolimus.

Resource links provided by NLM:


Further study details as provided by Hospital Universitari de Bellvitge:

Primary Outcome Measures:
  • To evaluate the effect of the administration of Rapamune on a clinical composite variable (change in proteinuria, blood pressure and hematuria) in patients with IgA nephropathy with poor prognosis criteria [ Time Frame: at month 12th ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in the glomerular filtrate rate evaluated by means of radionuclide techniques (51Cr-EDTA) and comparison between both arms [ Time Frame: At months 6th and 12th ] [ Designated as safety issue: No ]
  • Change in renal histology [ Time Frame: At 12 months ] [ Designated as safety issue: No ]
  • Percentage of patients who withdraw from the study medication due to adverse events [ Time Frame: Within 1 year ] [ Designated as safety issue: Yes ]
  • Percentage of patients with therapeutic failure [ Time Frame: Within 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 23
Study Start Date: January 2006
Study Completion Date: February 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A Drug: ACE inhibitor + statin
sirolimus starting at 1 mg/d (target 3-6 ng/ml) plus enalapril starting at 5 mg/d to control blood pressure plus atorvastatin starting at 10 mg/d
Experimental: B Drug: Sirolimus (study drug)+ACE inhibitor + statin
enalapril starting at 5 mg/d in order to control blood pressure. Atorvastatin starting at 10 mg/d

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 to 70 and with capacity to grant informed consent
  • Biopsy-proven IgA nephropathy by means of standard immunohistochemical and morphological criteria
  • Renal biopsy in the in the 3 months prior to randomization date
  • Absence of known hepatic, cardiac, pulmonary or intestinal disease
  • Glomerular filtrate estimated by Cockcroft-Gault, more than 30 ml/min
  • Any of the following clinical states: a) High blood pressure defined as systolic blood pressure higher than 140 mmHg or diastolic blood pressure higher than 90 mmHg associated with proteinuria between 0.3-1 g/day and/or microhematuria. b) Proteinuria higher than 1g/day
  • Women of child-bearing age will follow a suitable contraceptive method, and a negative pregnancy test will be needed before inclusion in the study

Exclusion Criteria:

  • Serology positive for HIV or hepatitis B infection (defined as positive for the HbsAg antigen) or hepatitis C infection (defined as viral RNA detection)
  • Treatment with steroids or immunosuppressors in the two previous years
  • Evidence of active infection at the time of inclusion in the study
  • Pregnancy or breastfeeding at the time of inclusion in the study
  • Estimated glomerular filtration < 30 ml/min, bilirubin > 2 mg/dl, or ALT or AST two times higher than the normal upper limit
  • Diabetes Mellitus, defined as patients treated with insulin or oral antidiabetics or glycemias higher than 140 mg/dl in two or more episodes
  • Poor control of high blood pressure (defined as systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg, taking 3 or more antihypertensives) or evidence or suspicion of renovascular disease
  • Thrombocytopenia less than 100,000 /mm3 or total neutrophil value lower than 2000 /mm3 or triglycerides value > 400 mg/dL (4.6 mmol/L) or cholesterol > 300 mg/dL (7.8 mmol/L) or LDL > 200 mg/dL
  • IgA nephropathy systemic forms, i.e., Schönlein-Henoch purpura, IgA nephropathy secondary forms, post-renal transplant IgA nephropathy recurrences, cases presented in the form of rapidly progressive renal failure and cases with the presence of cellular crescents in more than 50% of the glomeruli will be excluded
  • History of cancer in the previous 5 years,exception of skin basocellular carcinoma and uterine in situ carcinoma (completely removed both of them)
  • Know intolerance to Sirolimus or macrolides
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00396721

Locations
Spain
Nephrology Department. Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, Spain, 08907
Sponsors and Collaborators
Josep m Cruzado
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
Study Chair: Josep M Cruzado, Medical Doctor Nephrlogy Department. Hospital Universitari de Bellvitge
Principal Investigator: Meritxell Ibernon, MD HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL
Principal Investigator: JORDI BALLARÍN, MD FUNDACIÓ PUIGVERT DE BARCELONA
  More Information

Additional Information:
Publications:
Responsible Party: Josep m Cruzado, Nephrologist, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier: NCT00396721     History of Changes
Other Study ID Numbers: SIREPNA/05, 2005-002610-37
Study First Received: November 3, 2006
Last Updated: September 14, 2011
Health Authority: Spain: Ministry of Health

Keywords provided by Hospital Universitari de Bellvitge:
Nephropathy, IGA
Pilot trial
Sirolimus
Rapamune

Additional relevant MeSH terms:
Glomerulonephritis
Glomerulonephritis, IGA
Kidney Diseases
Nephritis
Urologic Diseases
Autoimmune Diseases
Immune System Diseases
Angiotensin-Converting Enzyme Inhibitors
Sirolimus
Everolimus
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents

ClinicalTrials.gov processed this record on April 17, 2014