Timely Recovery After Subclinical Heart Failure (TREASURE)

Timely Recovery After Subclinical Heart Failure (TREASURE Trial)

The goal of this randomized controlled trial is to assess the effectiveness of ACE inhibitors versus standard care) in reversing asymptomatic heart failure (HF stage-B) and/or diastolic dysfunction during a two-year open-label treatment period for formerly preeclamptic women on:

1. Reversibility of structural and functional myocardial impairment in asymptomatic HF towards healthy values;
2. The progression from asymptomatic to symptomatic HF (symptoms scored based on the NYHA criteria);
3. Cardiovascular performance (volume- and pressure load), cardio metabolic risk factors (glucose metabolism, lipid status, kidney function) and quality of life (questionnaires);
4. Novel biomarkers and relevant microRNA's indicative for hypertrophy, fibrosis inflammation and ischemia.

Eligible subjects will be counselled and upon informed consent randomized for either medication group (n=65) or care as usual group (n=65). After a complete cardiovascular assessment, medication will be initiated open-labeled (Perindopril 2 mg or no medication). Thereafter, standard medical check-ups (blood pressure, ECG, kidney function, transthoracic cardiac ultrasound, endothelial function, quality of life questionnaires, medical history taking, blood and urine banking) will be performed every six months for two years.

Researchers will compare ACE inhibitor (Perindopril 2 mg) and care as usual (i.e. no medication) to investigate whether ACE inhibitor allows timely recovery after subclinical heart failure.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Diastolic Dysfunction
• Intervention / Treatment: Drug: Perindopril

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6202AZ
      • Recruiting
      • AZMaastricht
      • Contact: Marc Spaanderman, Prof; Phone Number: +31(0)43-3874145; Email: zenab.mohseni@mumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All women who visit Maastricht Univeristy Medical Center+ for Cardiovascular screening with subclinical/asymptomatic heart failure (HF stage-B) and/or diastolic dysfunction;
• Aged 18 years and older;
• Premenopausal women with a history of preeclamptic pregnancy and premenopausal women with a history of normal pregnancy;
• Between 0.5 and 30 years postpartum;

Exclusion Criteria:

• Intention to pursue pregnancy within 2 years;
• Already using antihypertensive medication;
• Suffering diabetes mellitus, kidney failure (GFR<60 ml/min/1.73m2), pre-existent auto-immune disease and/or liver insufficiency;
• Breastfeeding during participation;
• Previous angio-edema

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group (Perindopril 2 mg); Eligible subjects will be counselled and upon informed consent randomized for either medication or care as usual (i.e. no medication). After a complete cardiovascular assessment, medication will be initiated open-labeled (Perindopril 2 mg or no medication). In case of side effects Perindopril will be replaced by Valsartan 40 mg twice daily. A blood pressure below 120/80 mmHg is targeted. Blood pressure will be measured once per two weeks until the targeted blood pressure is achieved or until medication dosage has increased 4 times, corresponding Perindopril 10mg as maximum dosage or corresponding Valsartan 320mg (160 mg twice daily) as maximum dosage.	Drug: Perindopril; In case of side effects Perindopril will be replaced by Valsartan; Other Names: Valsartan
No Intervention: Standard care group (i.e. no medication); Eligible subjects will be counselled and upon informed consent randomized for either medication or care as usual (i.e. no medication).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
No left Ventricular Hypertrophy	Left ventricular mass index <95 g/m2	From enrollment to the end of treatment after 2 years
No concentric remodeling	Relative Wall Thickness ≤0.43	From enrollment to the end of treatment after 2 years
No impaired systolic function	Left ventricular ejection fraction ≥55%	From enrollment to the end of treatment after 2 years
Normal diastolic function	Septal e'≥8 and Lateral e'≥10 and Average e'≥9 and LA <34 cc/m2	From enrollment to the end of treatment after 2 years

Collaborators and Investigators

• Sponsor: Academisch Ziekenhuis Maastricht
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development

Study record dates

Study Major Dates

• Study Start (Estimated): March 26, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: February 26, 2024
• First Submitted That Met QC Criteria: March 25, 2024
• First Posted (Actual): April 2, 2024

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: treatment; hypertension; heart failure; Pre-Eclampsia
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Valsartan; Perindopril
• Other Study ID Numbers: 2022-503135-33-00 (Other Identifier: EU trial 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