Study of the effect of serelaxin on high-sensitivity cardiac troponin I (hs cTnI) release in patients with chronic heart failure

• Register: EUCTR
• Last refreshed on: 11 December 2017
• Main ID: EUCTR2015-002673-38-DE
• Date of registration: 01/10/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Study of the effect of serelaxin on high-sensitivity cardiac troponin I (hs cTnI) release in patients with chronic heart failure
• Scientific title: 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
• Date of first enrolment: 26/11/2015
• Target sample size: 125
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002673-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Switzerland, United Kingdom

Contacts

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provide written informed consent before any assessment is performed.
2. Male or female = 18 years of age, with body weight = 160 Kg.
3. Diagnosis of stable CHF:
- New York Heart Association (NYHA) functional Class II/III.
- Receiving guideline-recommended treatment for CHF.
4. Left ventricular ejection fraction < 50%, obtained within the last 3 months prior to screening.
5. NT-proBNP > 250 ng/L in sinus rhythm or > 750 ng/L if not in sinus rhythm (determined locally).
6. Ability to exercise for at least 10 to 12 minutes based on investigator's judgment.
7. Systolic BP = 125 mm Hg at screening.
8. Renal function defined as an eGFR of = 25 mL/min/1.73 m2 at screening (sMDRD formula).
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 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
1. Dyspnea primarily due to non-cardiac causes.
2. Increased risk of developing hypotension during vasodilator therapy according to investigators judgement.
3. Any contraindication for exercise testing and spirometry.
4. 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.
5. Change in guideline-recommended CHF treatment within 1 month prior to screening.
6. Clinical evidence of acute coronary syndrome within 90 days prior to enrollment.
7. Significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate < 45 beats per minute or atrial fibrillation/flutter with sustained ventricular response of > 90 beats per minute at rest.
8.Severe renal impairment defined as eGFR < 25 mL/min/1.73m2 before randomization.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Chronic Heart Failure
MedDRA version: 19.1 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 100000004849

Intervention(s)

Product Name: serelaxin
Product Code: RLX030
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: SERELAXIN
Current Sponsor code: RLX030
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1.0-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: at 0, 132, 180, 240, 300, 360, 420 minutes

Primary end point(s): determine changes in plasma concentrations of hs cTnI following a cardiac stress test

Main Objective: To evaluate the effect of short-term i.v. administration of serelaxin in CHF patients on the geometric mean of hs-cTnI concentrations compared to placebo (both in addition to SoC) after an exercise testing session.

Secondary Objective: - To evaluate the effect of short-term i.v. administration of serelaxin in CHF patients on the geometric mean of hs-cTnI concentrations compared to placebo at 4 and 5 hours after the start of an exercise testing session.
- To evaluate the effect of short-term i.v. administration of serelaxin in CHF patients on the geometric mean of N terminal pro-brain natriuretic peptide (NT-proBNP) concentrations after an exercise testing session.
- To evaluate the effect of short-term i.v. administration of serelaxin in CHF patients on the geometric mean of heart-type fatty acid-binding protein (H-FABP).
- To evaluate the safety and tolerability of i.v. serelaxin in CHF patients.

Secondary Outcome(s)

Secondary end point(s): - Determine changes in plasma concentrations of hs cTnI, NT-proBNP and H-FABP following a cardiac stress test. (efficacy)
- ECG, Physical examination, vital signs, Laboratory evaluation, Clinical chemistry, Hematology (safety)

Timepoint(s) of evaluation of this end point: - efficacy: at 0, 132, 180, 240, 300, 360, 420 minutes
- safety: at screening and start of the infusion for both treatment period as well as at Day 29 (follow up period 15 days after treatment period 2)

Secondary ID(s)

CRLX030A2211

2015-002673-38-GB

Source(s) of Monetary Support

Novartis Pharma Services AG