Study of the Effect of Serelaxin on High-sensitivity Cardiac Troponin I (Hs-cTnI) Release in Patients With Chronic Heart Failure

Phase 2

Terminated

Conditions: Chronic Heart Failure

Interventions: Drug: Serelaxin
Drug: Placebo

Registration Number: NCT02625922

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This was a multicenter, randomized, double-blind, crossover, placebo-controlled, Phase II clinical study that evaluated the effect of serelaxin versus placebo (both in addition to SoC) on the release of hs-cTnI, in patients with CHF after an exercise testing session.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 26

Inclusion Criteria

Male or female ≥ 18 years of age, with body weight ≤ 160 Kg
Diagnosis of stable CHF:
- New York Heart Association (NYHA) functional Class II/III.
- Receiving guideline-recommended treatment for CHF.
Left ventricular ejection fraction < 45%, obtained within the last 3 months prior to screening.
NT-proBNP > 300 ng/L in sinus rhythm or > 900 ng/L if not in sinus rhythm (determined locally).
Ability to exercise for at least 10 to 12 minutes based on investigator's judgment.
Systolic BP ≥ 125 mmHg at randomization
Renal function defined as an eGFR of ≥ 25 mL/min/1.73 m^2 at screening (sMDRD formula).

Key

Exclusion Criteria

Dyspnea primarily due to non-cardiac causes.
Increased risk of developing hypotension during vasodilator therapy according to investigators judgement.
Any contraindication for exercise testing and spirometry.
Stopping of the spiroergometry at screening according to the stopping rules, unless the patient has reached maximum exercise capacity defined as carbon dioxide production/oxygen consumption (VCO2/VO2) > 1.05.
Change in guideline-recommended CHF treatment within 1 month prior to screening.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo followed by Serelaxin	Serelaxin	On Day 1 of treatment period 1, matching placebo will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen The routine exercise assessment will commence at minute 120. In treatment period 2, on day 15 ± 1-day washout, Serelaxin will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen.
Serelaxin followed by Placebo	Serelaxin	On Day 1 of treatment period 1, Serelaxin will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen The routine exercise assessment will commence at minute 120. In treatment period 2, on day 15 ± 1-day washout, matching placebo will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen.
Serelaxin followed by Placebo	Placebo	On Day 1 of treatment period 1, Serelaxin will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen The routine exercise assessment will commence at minute 120. In treatment period 2, on day 15 ± 1-day washout, matching placebo will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen.
Placebo followed by Serelaxin	Placebo	On Day 1 of treatment period 1, matching placebo will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen The routine exercise assessment will commence at minute 120. In treatment period 2, on day 15 ± 1-day washout, Serelaxin will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen.

Primary Outcome Measures

Name	Time	Method
Geometric Mean of High Sensitivity Cardiac Troponin I (Hs-cTnI) Concentration After Exercise Compared to Placebo	Baseline, up to 7 hours after the start of an exercise testing session on treatment period 1 (Day 1) and treatment period 2 (Day 15+/- 1)	This cardiac biomarker measurement was obtained to determine plasma concentrations following a cardiac stress test.

Secondary Outcome Measures

Name	Time	Method
Geometric Mean of High Sensitivity Cardiac Troponin I (Hs-cTnI) Concentrations After Exercise Compared to Placebo at 4 and 5 Hours	4 and 5 hours after exercise testing session	This cardiac biomarker measurement was obtained to determine plasma concentrations following a cardiac stress test.
Log-transformed Concentration of N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Concentrations Compared to Placebo	Baseline, up to 7 hours after the start of an exercise testing session on treatment period 1 (Day 1) and treatment period 2 (Day 15 +/- 1)	This cardiac biomarker measurement was obtained to determine plasma concentrations following a cardiac stress test.
Log-transformed Concentration Values of Heart-type Fatty Acid-binding Protein (H-FABP) Concentrations Compared to Placebo	Baseline, up to 7 hours after the start of an exercise testing session on treatment period 1 (Day 1) and treatment period 2 (Day 15 +/- 1)	This cardiac biomarker measurement was obtained to determine plasma concentrations following a cardiac stress test.