The PIROUETTE trial

Phase 2

Completed

• Conditions: Specialty: Cardiovascular disease, Primary sub-specialty: Heart Failure; UKCRC code/ Disease: Cardiovascular/ Other forms of heart disease; Circulatory System; Myocardial fibrosis

• Registration Number: ISRCTN91621241
• Lead Sponsor: niversity Hospital of South Manchester NHS Foundation Trust

Brief Summary

2021 Results article in https://doi.org/10.1038/s41591-021-01452-0 (added 31/08/2021)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-01-11
• Study Completion: 2020-04-07
• Last Update Posted: 13 September 2021

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 94

Inclusion Criteria

1. Written informed consent
2. Male or female; aged 40 years or older
3. HF, defined as one symptom (dyspnoea on exertion,orthopnoea or paroxysmal nocturnal dyspnoea) present at the time of screening, and one sign (peripheral oedema, crackles on chest auscultation post-cough, raised jugular venous pressure or chest x-ray demonstrating pleural effusion, pulmonary congestion, or cardiomegaly) present at the time of screening or in the previous 12 months
4. LVEF > 45% at Visit 0
5. BNP = 100 pg/ml or NTproBNP = 300 pg/ml at Visit 0. For patients in atrial fibrillation on Visit 0 ECG, BNP > 300pg/ml or NTproBNP > 900 pg/ml at Visit 0

In order to be randomised, patients must also have myocardial fibrosis, defined as ECM volume > 27% by CMR at Visit 0.

Exclusion Criteria

1. Myocardial infarction, coronary artery bypass graft surgery or percutaneous coronary intervention within the previous 6 months.
2. Probable alternative cause of patient’s HF symptoms that in the opinion of the investigator primarily accounts for patient’s dyspnoea such as significant pulmonary disease, anaemia or obesity. Specifically, patients with the below are excluded:
2.1. Severe chronic obstructive pulmonary disease (COPD) (i.e., requiring home oxygen, chronic nebuliser therapy,or chronic oral steroid therapy), or
2.2. Haemoglobin < 9 g/dl, or
2.3. Body mass index (BMI) > 55 kg/m2
3. Known pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative cardiomyopathy
4. Clinically significant congenital heart disease
5. Presence of severe valvular heart disease
6. Atrial fibrillation or flutter with a resting ventricular rate > 100bpm
7. Any medical condition, which in the opinion of the Investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study
8. Severe renal dysfunction at Visit 0, defined as eGFR <30 mL/min, or end-stage renal disease requiring dialysis
9. History of severe hepatic impairment or liver dysfunction at Visit 0, defined as total bilirubin above the ULN (excluding patients with Gilbert’s syndrome), AST or ALT >3 times the ULN or alkaline phosphatase >2.5 times the ULN.
10. Prolonged corrected QT interval, defined as a corrected QT interval >500 msec on ECG using Bazett formula
11. Known hypersensitivity to any of the components of the IMP
12. Use of other investigational drugs at the time of enrolment, or within 30 days or 5 half-lives of enrolment, whichever is longer.
13. Fluvoxamine use 28 days prior of Visit 0
14. Contraindication to MRI scanning or gadolinium-basedcontrast agent
15. Pregnancy, lactation or planning pregnancy

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Absolute change in myocardial ECM volume is measured using cardiovascular magnetic resonance (CMR) scanning at baseline and 52 weeks