The Effect of Ramipril in Suppressing ST2 Expression in Rheumatic Mitral Stenosis Patients

NCT03991910 | Unknown Phase 3 DMC

• 1 other identifier: RamiRHeD
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

Objective propose: to investigate the effect of Ramipril in suppressing ST2 (suppression of tumorigenicity 2) in the cardiac mitral valve in patients with Rheumatic Heart Disease. We hypothesized that we hypothesized that ramipril will improve rheumatic mitral valve fibrosis through the downregulation of ST2.

Conditions

Rheumatic Heart Disease; Mitral Stenosis; Rheumatic Mitral Stenosis; Fibrosis; Heart; ACE Inhibitor

Keywords

Rheumatic Heart Disease; Mitral Stenosis; Rheumatic Mitral Stenosis; Valve Fibrosis; ramipril; ST2

Outcome Measures

Primary Outcomes (1)

• ST2 expression in mitral valve tissue and papillary muscle

  expression of ST2 in mitral valve tissue, using immunohistochemistry method

  a year

Secondary Outcomes (13)

• ST2 Plasma concentration

  a year

• NT-proBNP concentration (pg/ml)

  a year

• NYHA class

  a year

• cardiovascular mortality

  1 year

• All-cause mortality

  1 year

Study Arms (2)

control

PLACEBO COMPARATOR

control patients will be given a placebo

Drug: Placebos

treatment

EXPERIMENTAL

Ramipril 5 mg treatment group

Drug: Ramipril 5Mg Oral Capsule

Interventions

Placebos DRUG

the control group will be given placebo inside a capsule, so study participant won't be able to know the drug and doses inside the capsule (for masking). Placebo will be given until 5 days prior to Mitral valve replacement surgery.

Also known as: control group

control

Ramipril 5Mg Oral Capsule DRUG

the treatment group will be given each Ramipril 2,5 mg inside a capsule as an initial dose, for 2 weeks. If there is no serious adverse effect in the observation period of 2 weeks, Ramipril 5 mg inside a capsule will be given for the next weeks until 5 days before the mitral valve surgery date. Study participant won't be able to know the drug and doses inside the capsule (for masking)

Also known as: treatment group

treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with mitral valve stenosis or a combination
• aged more than 18 years
• undergo cardiac valve replacement operation with or without a tricuspid valve repair,
• patients with systolic blood pressure (SBP) ≥ 100 mmHg and diastolic blood pressure (DBP) ≥ 60 mmHg
• passed in medication phase without side effect minimum 4 weeks until operation schedule

You may not qualify if:

• Patients with congenital heart disease
• patients with non-mitral valve surgery
• patients with coronary artery bypass surgery
• patients who refuse to join this study.
• adults aged over 65 years or older
• pregnant women
• patients with autoimmune disease.
• Patients with persistent hypotension (systolic blood pressure (BP) \< 100 mm Hg)
• severe aortic stenosis (aortic valve orifice \< 0.75 cm2 )
• chronic renal dysfunction with serum creatinine \> 2.5 mg/ dL,
• known ACEI intolerance.

Sponsors & Collaborators

• Indonesia University: lead

Study Sites (1)

Ade Meidian Ambari

Jakarta, DKI Jakarta, 1140, Indonesia

RECRUITING

Related Publications (5)

• Wei Q, Liu H, Liu M, Yang C, Yang J, Liu Z, Yang P. Ramipril attenuates left ventricular remodeling by regulating the expression of activin A-follistatin in a rat model of heart failure. Sci Rep. 2016 Sep 19;6:33677. doi: 10.1038/srep33677.

  PMID: 27642098 BACKGROUND

• Shi Q, Abusarah J, Baroudi G, Fernandes JC, Fahmi H, Benderdour M. Ramipril attenuates lipid peroxidation and cardiac fibrosis in an experimental model of rheumatoid arthritis. Arthritis Res Ther. 2012 Oct 18;14(5):R223. doi: 10.1186/ar4062.

  PMID: 23079082 BACKGROUND

• Ciccone MM, Cortese F, Gesualdo M, Riccardi R, Di Nunzio D, Moncelli M, Iacoviello M, Scicchitano P. A novel cardiac bio-marker: ST2: a review. Molecules. 2013 Dec 11;18(12):15314-28. doi: 10.3390/molecules181215314.

  PMID: 24335613 BACKGROUND

• Ambari AM, Setianto B, Santoso A, Radi B, Dwiputra B, Susilowati E, Tulrahmi F, Doevendans PA, Cramer MJ. Angiotensin Converting Enzyme Inhibitors (ACEIs) Decrease the Progression of Cardiac Fibrosis in Rheumatic Heart Disease Through the Inhibition of IL-33/sST2. Front Cardiovasc Med. 2020 Jul 28;7:115. doi: 10.3389/fcvm.2020.00115. eCollection 2020.

  PMID: 32850979 BACKGROUND

• Ambari AM, Setianto B, Santoso A, Radi B, Dwiputra B, Susilowati E, Tulrahmi F, Wind A, Cramer MJM, Doevendans P. Randomised controlled trial into the role of ramipril in fibrosis reduction in rheumatic heart disease: the RamiRHeD trial protocol. BMJ Open. 2021 Sep 13;11(9):e048016. doi: 10.1136/bmjopen-2020-048016.

  PMID: 34518254 DERIVED

MeSH Terms

Conditions

Rheumatic Heart Disease; Mitral Valve Stenosis; Fibrosis

Interventions

Control Groups; Ramipril

Condition Hierarchy (Ancestors)

Rheumatic Fever; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ade Meidian Ambari, MD,FIHA

  Universitas Indonesia, RSPJN harapan kita

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ade Meidian Ambari, MD, FIHA

CONTACT

021-5684085; dr_ade_meidian@yahoo.co.id

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: study participants do not know whether they become treatment group or control group the investigator does not know which participant in each group
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, cardiologist, head of cardiovascular prevention and rehabilitation

Model Details: pre post test design with placebo control

Study Record Dates

• First Submitted: June 17, 2019
• First Posted: June 19, 2019
• Study Start: June 27, 2019
• Primary Completion: August 8, 2024
• Study Completion: August 8, 2024
• Last Updated: August 16, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)