Randomised, Double-Blind, Placebo-Controlled, Multi-Center, Sequential Cohort Study to Evaluate the Effect of SLV320 in Addition to Chronic Furosemide Treatment on Renal Function in Subjects with Congestive Heart Failure and Impaired Renal Function.Estudio de Cohortes Secuenciales, Aleatorizado, Doble Ciego,Controlado con Placebo y Multicéntrico para evaluar el Efecto de SLV320 añadido al tratamiento crónico con Furosemida sobre la función renal en pacientes con Insuficiencia Cardiaca Congestiva y Función Renal Alterada

• Conditions: Renal Function in Subjects with Congestive Heart Failure and Impaired Renal Function who are on Chronic Furosemide Treatment; MedDRA version: 9.1Level: LLTClassification code 10010684Term: Congestive heart failure

• Registration Number: EUCTR2007-000490-40-ES
• Lead Sponsor: Solvay Pharmaceuticals GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-06-04
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

Subjects must meet all of the following criteria to be included in the study:
1.Men and women aged 18 years to 85 years.
2.Informed consent must be obtained from each subject before any study-related procedure is performed.
3.Subjects must have a history of chronic, symptomatic NYHA Class II-III CHF and impaired renal function (baseline eGFR of 20 to 75 mL/min/1.73m2) for at least 3 months before Visit 1 (Day 1).
The Modification of Diet in Renal Disease (MDRD) equation to estimate GFR can be found on page 37 of the protocol (22 Mar 2007)
4.Subjects must be on chronic treatment with furosemide =40 mg daily for at least 3 weeks before Visit 1 (Day 1).
5.Subjects should be receiving optimal doses of standard CHF therapies (for example ACE inhibitors, beta-blockers, angiotensin receptor blockers (ARB), hydralazine, isosorbide dinitrate and/or digitalis). Subjects must have been on a stable dose of these medications for at least 4 weeks before Visit 1 (Day 1). Subjects receiving hydralazine and/or isosorbide dinitrate should have been treated with these drugs for at least 3 months before Visit 1 (Day 1).
Subjects should be taking both an ACE inhibitor (or ARB) and a beta-blocker, unless there is intolerance or a contraindication or another medical reason, which must be documented. Subjects should have been treated with these drugs for at least 3 months before Visit 1 (Day 1). They must also have been taking a stable dose for at least 4 weeks before Visit 1 (Day 1).
Subjects treated with amiodarone must also have been taking a stable dose for at least 4 weeks before Visit 1 (Day 1).
6.The subject must be male, female of non-childbearing potential or female of childbearing potential with an accepted birth control method.
Females with childbearing potential may be enrolled providing that:
-She is routinely using a medically accepted method of birth control. Medically accepted methods of birth control are defined as the use of either a contraceptive implant, a contraceptive injection, an intra-uterine device or an oral contraceptive for at least 3 months before Visit 1 (Day 1), and which she agrees to continue using during the study, or a double-barrier method which has to consist of a combination of any two of the following: diaphragm, cervical cap, condom, or spermicide.
-She agrees not to attempt at becoming pregnant during the study.
-A female of non-childbearing potential is defined as one who has been post-menopausal for at least 24 months, was surgically sterilized (bilateral tubal ligation) or had a hysterectomy prior to screening.
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.Any female of childbearing potential without adequate contraception. Any female who is pregnant or breastfeeding.
2.The subject's condition is so unstable that he / she may require hospitalization (for cardiovascular disease) or adjustment of background medications for CHF.
3.Hospitalization within 7 days before Visit 1 (Day 1).
NB:A subject who was recently discharged from the hospital (less than 7 days) may not be randomized at that time, but may be reconsidered for Visit 1 (Day 1), after he / she is stabilized for at least 7 days.
4.Evidence of any significant respiratory, urogenital, gastro-intestinal, hepatic, hematological, immunologic, head, ears, eyes, nose, throat (HEENT), dermatologic, connective tissue, musculoskeletal, metabolic, nutritional, endocrine, neurological, psychiatric diseases, allergy, major surgery or other relevant diseases as revealed by history, physical examination and / or laboratory assessments which might limit participation in or completion of the study.
5.Recent or chronic gastro-intestinal, hepatic, or biliary disorder that could impair absorption, metabolism, or excretion of orally administered medication.
6.Subjects with malignant tumors with a short life expectancy and / or severe infection.
7.Concomitant use of other investigational drugs or use of any investigational agent within 30 days before Visit 1 (Day 1), and within at least 10 half-life times of that agent before Visit 1 (Day 1).
8.Any history of a severe abnormal medication reaction.
9.Subjects with fever of = 38°C.
10.Subjects with significant liver disease or with serum transaminase concentrations (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) more than three times the upper limit of the normal reference range.
11.Subjects with uncontrolled diabetes (fasting serum glucose > 11 mmol/L [> 197 mg/dL]).
12.Subjects with eGFR < 20 mL/min/1.73m2 calculated by the MDRD equation.
The MDRD equation to estimate GFR can be found on page 38 of the Protocol (Date: 22 Mar 2007)
13.Subjects with serum potassium < 3.5 mmol/L or > 5.5 mmol/L.
14.Subjects with hemoglobin of < 9 g/dL (< 90 g/L) or hematocrit of < 30%.
15.Subjects with bilateral renal artery stenosis (from medical history).
16.Any history of a convulsive disorder or pre-convulsive state and any risk for a convulsive disorder or pre-convulsive state (for example any past brain trauma, abuse of alcohol etcetera).
17.Subjects may not be related to the Investigator in any way (family relation, practice workers etcetera).
18.Inability to return for scheduled visits.
19.Any condition associated with poor compliance including alcoholism, mental illness or medication dependence. Inability of the subject to understand and follow the requirements of the protocol in the language of the Investigator.
20.Any other reason, in the Investigator’s opinion, that prohibits inclusion of the subject into the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified