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
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: 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
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents

ClinicalTrials.gov processed this record on August 28, 2014