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

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter, Randomized, Double-blind, Crossover Placebo-controlled Phase II Study to Assess the Effect of Serelaxin Versus Placebo on High-sensitivity Cardiac Troponin I (Hs-cTnI) Release in Patients With Chronic Heart Failure After Exercise When Used in Addition to Standard of Care

Conditions
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Chronic Heart Failure

Intervention / Treatment
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* Drug: Serelaxin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Serelaxin followed by Placebo<br>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. | Drug: Serelaxin<br>* Serelaxin will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen<br>* Other names: RLX030;Drug: Placebo<br>* Matching placebo i.v infusion<br>|
| Experimental: Placebo followed by Serelaxin<br>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. | Drug: Serelaxin<br>* Serelaxin will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen<br>* Other names: RLX030;Drug: Placebo<br>* Matching placebo i.v infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean of High Sensitivity Cardiac Troponin I (Hs-cTnI) Concentration After Exercise Compared to Placebo | This cardiac biomarker measurement was obtained to determine plasma concentrations following a cardiac stress test. | 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean of High Sensitivity Cardiac Troponin I (Hs-cTnI) Concentrations After Exercise Compared to Placebo at 4 and 5 Hours | This cardiac biomarker measurement was obtained to determine plasma concentrations following a cardiac stress test. | 4 and 5 hours after exercise testing session | 
| Log-transformed Concentration of N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Concentrations Compared to Placebo | This cardiac biomarker measurement was obtained to determine plasma concentrations following a cardiac stress test. | 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) | 
| Log-transformed Concentration Values of Heart-type Fatty Acid-binding Protein (H-FABP) Concentrations Compared to Placebo | This cardiac biomarker measurement was obtained to determine plasma concentrations following a cardiac stress test. | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Serelaxin,, Chronic heart failure,, Spiroergometry,, Troponin,, New York Heart Association (NYHA) functional Class II/III,, Left ventricular ejection fraction,