PILOT TRIAL OF TREATMENT OF POOR-PROGNOSIS IgA NEPHROPATHY WITH LOW EXPOSURE TO SIROLIMUS. Ensayo clínico piloto de tratamiento de la nefropatía IgA con factores de mal pronóstico con dosis bajas de sirolimus

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-002610-37-ES
• Date of registration: 30/09/2005
• Prospective Registration: Yes
• Primary sponsor: NEPHROLOGY DEPARTMENT (HOSPITAL UNIVERSITARY OF BELLVITGE)
• Public title: PILOT TRIAL OF TREATMENT OF POOR-PROGNOSIS IgA NEPHROPATHY WITH LOW EXPOSURE TO SIROLIMUS. Ensayo clínico piloto de tratamiento de la nefropatía IgA con factores de mal pronóstico con dosis bajas de sirolimus
• Scientific title: PILOT TRIAL OF TREATMENT OF POOR-PROGNOSIS IgA NEPHROPATHY WITH LOW EXPOSURE TO SIROLIMUS. Ensayo clínico piloto de tratamiento de la nefropatía IgA con factores de mal pronóstico con dosis bajas de sirolimus
• Date of first enrolment: 05/12/2005
• Target sample size: 30
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-002610-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Standard therapy

Countries of recruitment

Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1.Age 18 to 70 and with capacity to grant informed consent
2. Biopsy-proven grade II or III IgA nephropathy by means of standard immunochistochemical and morphological criteria (see Annex 4).
3. Renal biopsy in the in the 3 months prior to randomization date.
4. Absence of known hepatic, cardiac, pulmonary or intestinal disease
5. Mild renal failure: glomerular filtrate estimated by Cockroft-Gault, more than 60 ml/min.
6. 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 wit proteinuria between 0.3-1 g/day and/or microhematuria.
b) Proteinuria higher than 1g/day.
7. Women of child-bearing age will follow a suitable contraceptive method, and a negative pregnancy test will be needed before inclusion in the study

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Serology positive for HIV or hepatitis B infection (defined as positive for the HbsAg antigen) or hepatitis C infection (defined as viral RNA detection)
2. Treatment with steroids or immunosuppressors in the two previous years.
3. Evidence of active infection at the time of inclusion in the study.
4. Pregnancy or lactancy at the time of inclusion in the study..
5. Estimated glomerular filtration < 60 ml/min, bilirrubine > 2 mg/dl, or ALT or AST two times higher than the normal upper limit.
6. Diabetes Mellitus, defined as patients treated with insulin or oral antidiabetics or glucaemias higher than 140 mg/dl in two or more episodes.
7. 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.
8. 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.
9. 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Intervention(s)

Trade Name: RAPAMUNE
Product Name: SIROLIMUS
Pharmaceutical Form: Oral solution
INN or Proposed INN: Sirolimus
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Trade Name: RAPAMUNE
Product Name: SIROLIMUS
Pharmaceutical Form: Tablet
INN or Proposed INN: Sirolimus
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: RAPAMUNE
Product Name: SIROLIMUS
Pharmaceutical Form: Tablet
INN or Proposed INN: Sirolimus
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

Primary end point(s): -Change in a composite clinical variable resulting from evolution of proteinuria figures measured at months 6th and 12th, blood pressure measured at month 6th and 12th and hematuria at month 6th and 12th.

Main Objective: To evaluate the effect at month 12th 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.

Secondary Objective: a) Change in the glomerular filtrate rate evaluated by means of radionuclide techniques (51Cr-EDTA) at months 6th and 12th, and comparison between both arms.
b) Change in renal histology at 12 months.
c) Percentage of patients who withdraw from the study medication due to adverse events.
d) Percentage of patients with therapeutic failure

Secondary ID(s)

SIREPNA/05