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

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Heart Failure
• Intervention / Treatment: Drug: Serelaxin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Muenchen, Germany, 81675
    • Novartis Investigative Site
  • Muenchen, Germany, 80636
    • Novartis Investigative Site
  • Mecklenburg Vorpommern
    • Greifswald, Mecklenburg Vorpommern, Germany, 17475
      • Novartis Investigative Site
• Switzerland
  • Basel, Switzerland, 4031
    • Novartis Investigative Site
• United Kingdom
  • Hull, United Kingdom, HU16 5JQ
    • Novartis Investigative Site
  • London, United Kingdom, SW 6NP
    • Novartis Investigative Site
  • Tyne And Wear, United Kingdom, NE2 4HH
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Serelaxin followed by 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.	Drug: Serelaxin; Serelaxin will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen; Other Names: RLX030; Drug: Placebo; Matching placebo i.v infusion
EXPERIMENTAL: Placebo followed by 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.	Drug: Serelaxin; Serelaxin will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen; Other Names: RLX030; Drug: Placebo; Matching placebo i.v infusion

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: February 5, 2016
• Primary Completion (ACTUAL): January 11, 2017
• Study Completion (ACTUAL): January 11, 2017

Study Registration Dates

• First Submitted: December 3, 2015
• First Submitted That Met QC Criteria: December 7, 2015
• First Posted (ESTIMATE): December 9, 2015

Study Record Updates

• Last Update Posted (ACTUAL): September 21, 2018
• Last Update Submitted That Met QC Criteria: January 11, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Serelaxin,; Left ventricular ejection fraction,; Chronic heart failure,; Spiroergometry,; Troponin,; New York Heart Association (NYHA) functional Class II/III,
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CRLX030A2211; 2015-002673-38 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No