A clinical trial on the interaction between aliskiren and furosemide in patients with heart failure.

• Conditions: Essential hypertension; MedDRA version: 14.0Level: PTClassification code 10015488Term: Essential hypertensionSystem Organ Class: 10047065 - Vascular disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2008-006156-22-LT
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01-21
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

1. Males or females, aged between 18 and 75 years (inclusive) at screening.
2. Female patients of childbearing potential must be using an acceptable form of contraception, Postmenopausal females must have had no regular menstrual bleeding for at least one (1) year prior to screening.
Female patients who report surgical sterilization must have had the procedure at least six (6) months prior to screening.
3. All patients must be diagnosed at least 3 months prior to screening with either systolic or diastolic heart failure with signs and symptoms of congestive heart failure and NYHA functional class II to III symptoms AND be on stable medication for at least 12 weeks (furosemide only stable for 3 weeks).
4. A patient has to fulfill either a), or b) to qualify for participation.
(a) Patients with a documented left ventricular ejection fraction (LVEF) greater than 20% but lower than 40%.
(b) Patients with a documented left ventricular ejection fraction (LVEF) greater than 40% AND with a history of NT-pro-BNP > 400 pg/mL (or BNP > 100 pg/mL) within 12 months of screening.
5. Patients must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) of maximum 40 kg/m2.
6. Patients must be able to communicate well with the investigator, to understand and comply with the requirements of the study, and to understand and sign the written informed consent.

For a detailed list of inclusion criteria, please refer to the full protocol.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

Exclusion Criteria

1. Treatment with Angiotensin Receptor Blockers (ARBs), aldosterone receptor antagonists and diuretics (other than furosemide) within 3 weeks of first dose and during the study. Beta blockers are permitted providing the dose has been stable for at least 3 weeks before the first dose and remains so throughout the study.
2. Hypertrophic cardiomyopathy (HCMP).
3. If a subject is currently treated with furosemide, the dose must be stable for at least 3 weeks before the first dose and the dose must not exceed 60 mg daily. If a subject is not pre-treated with furosemide, this does not apply.
4. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase 2 (COX-2) inhibitors within 72 hours prior to first dose or during the 24 hour in-clinic study periods.
5. Treatment with sildenafil (Viagra), vardenafil (Levitra), or tadalafil (Cialis) within 72 hours prior to first dose or during the 24 hour in-clinic study periods.
6. Commencing any new medication during the conduct of the study that could affect renal function or serum creatinine.
7. Stable heart failure requiring treatment with both an ACE inhibitor and an ARB.
8. msSBP =160 mmHg and/or msDBP = 100mmHg and/or secondary forms of hypertension.
9. Persistent sitting systolic blood pressure <90 mmHg.
10. Signs or symptoms of dehydration (BUN/sCr ratio; orthostatic hypotension) as judged to be clinically significant by the investigator.
11. Uncontrolled diabetes based on the investigator’s clinical judgement, and glucose/HbA1c measurements.
12. History of angioedema.

For a full list of exclusion criteria, please refer to the full protocol.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: •To assess the effect of single (150 mg) and multiple (150 mg and 300 mg) doses of aliskiren on the diuretic efficacy (efficacy index) of 60 mg furosemide at steady state.;Secondary Objective: •To assess the effect of multiple doses of aliskiren (150 mg and 300 mg) on the pharmacokinetics of 60 mg furosemide.<br>•To assess the effect of multiple doses of aliskiren (150 mg and 300 mg) on blood pressure when co administered with 60 mg furosemide at steady state.<br>•To assess the effect of single and multiple doses of aliskiren (150 mg) on urinary sodium, urinary potassium, and creatinine clearance when co administered with 60 mg furosemide at steady state.<br>;Primary end point(s): - urinary sodium concentration in 0-4h and 0-24h urine collection fractions<br>- urine volume in 0-4h and 0-24h urine collection fractions<br>- urinary furosemide concentration in 0-4h and 0-24h urine collection fractions;Timepoint(s) of evaluation of this end point: Not applicable.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary end points not applicable according to the protocol design.;Timepoint(s) of evaluation of this end point: Not applicable.