Effect of ACE-Inhibition on Microvascular Function in Women With Assessed Microvascular Dysfunction

NCT02525081 | Completed Phase 4 DMC

• 1 other identifier: ACIM
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to explore effects of long term treatment with ACE-inhibitor on the small vessel function assessed by coronary flow reserve (CFR) by transthoracic echocardiography and flow mediated dilation in normotensive patients with small vessel disease (CFR\<2.2) and Angina Pectoris but no obstructive coronary artery disease.

Conditions

Microvascular Angina

Keywords

Microvascular Angina; therapy

Outcome Measures

Primary Outcomes (1)

• Change from baseline in coronary flow reserve to after intervention

  Coronary flow reserve is assessed by non-invasive Trans-Thoracic Doppler Echocardiography (TTDE)

  Patients are followed on average 6 months

Secondary Outcomes (6)

• Change from baseline in Seattle Angina Questionnaire to after intervention

  Patients are followed on average 6 months

• Change from baseline in Endothelial function to after intervention

  Patients are followed on average 6 months

• Change from baseline in Systolic function by speckle tracking strain to after intervention

  Patients are followed on average 6 months

• Change from baseline in Roses questionnaire to after intervention

  Patients are followed on average 6 months

• Change from baseline in Vital exhaustion questionnaire to after intervention

  Patients are followed on average 6 months

Study Arms (2)

ACE-inhibitor

EXPERIMENTAL

In both the placebo and Ramipril group medication will start with either 2,5 mg (Blood Pressure\<130) or 5 mg (Blood Pressure\>130) daily. After 2-3 weeks the dose is doubled to 5 mg or 10 mg unless blood pressure is below 115 mmHg. If blood pressure continues to be higher than 115 mmHg for patients up titrated to 5 mg treatment dose will be doubled to 10 mg at the third visit. Patients taking a dose of * 2,5 mg will take a half tablet a day * 5 mg will take one whole tablet a day * 10 mg will take two tablets a day

Drug: Ramipril (ACE-inhibitor)

Placebo

PLACEBO COMPARATOR

In both the placebo and Ramipril group medication will start with either 2,5 mg (Blood Pressure\<130) or 5 mg (Blood Pressure\>130) daily. After 2-3 weeks the dose is doubled to 5 mg or 10 mg unless blood pressure is below 115 mmHg. If blood pressure continues to be higher than 115 mmHg for patients up titrated to 5 mg treatment dose will be doubled to 10 mg at the third visit. Patients taking a dose of * 2,5 mg will take a half tablet a day * 5 mg will take one whole tablet a day * 10 mg will take two tablets a day

Drug: placebo

Interventions

Ramipril (ACE-inhibitor) DRUG

up to 10 mg

Also known as: Ramipril

ACE-inhibitor

placebo DRUG

up to 10 mg

Placebo

Eligibility Criteria

• Age: 18 Years - 86 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients from an established cohort of patients with non obstructive coronary artery disease
• Microvascular dysfunction defined as a transthoracic echocardiography measured coronary flow reserve (CFR) \< 2.2
• A good quality (quality index \> 3) examination
• A blood pressure ≤ 150 at last visit in iPower
• Patients who are not in treatment for documented hypertension

You may not qualify if:

• Current treatment with ACE-inhibitors or Angiotensin II-antagonists
• Atrial fibrillation
• Pace-maker
• Allergy towards Ace-inhibitor, Ramipril ® or tool-medicine: Dipyridamole/adenosine, Nitro-glycerine or rescue medicine: Theophylline
• Baseline CFR \>2.5 when entering ACIM-study.
• Coronary angiography with significant stenotic lesions (\>/=50%)
• Other cause of chest discomfort deemed highly likely
• Left ventricular ejection fraction below 45% assessed by echocardiography at baseline measurement
• Significant valvular heart disease (Definition: Verified in medical records after echocardiography. If the echocardiographer in this study suspects valvular heart disease, the patient is referred for expert evaluation and excluded from the study until valvular disease has been excluded. All definitions are taken from the guidelines of the Danish Society of Cardiology (DCS).
• Haemodynamic significant Aortic Stenosis: Valve area \< 1 cm2 or \<0.6 cm2/m2 body surface area.
• Severe aorta Regurgitation (AR): Vena contracta \> 6 mm, Moderate/severe left ventricle (LV) volume load, ERO \> 0.3 cm².
• Mitral Stenosis (MS): Valve area \< 2.5 cm2.
• Severe Mitral Regurgitation (MR): effective regurgitant orifice \> 0.4 cm², Moderate/severe LV-load, Vena contracta \> 6 mm.
• Congenital heart disease or cardiomyopathy verified in medical records
• Severe chronic obstructive pulmonary disease with forced expiratory volume in 1 second (FEV1)\<50% of predicted

Sponsors & Collaborators

• Bispebjerg Hospital: lead

Study Sites (1)

Bispebjerg Hospital

Copenhagen NV, 2400, Denmark

Location

Related Publications (1)

• Michelsen MM, Rask AB, Suhrs E, Raft KF, Host N, Prescott E. Effect of ACE-inhibition on coronary microvascular function and symptoms in normotensive women with microvascular angina: A randomized placebo-controlled trial. PLoS One. 2018 Jun 8;13(6):e0196962. doi: 10.1371/journal.pone.0196962. eCollection 2018.

  PMID: 29883497 DERIVED

MeSH Terms

Conditions

Microvascular Angina

Interventions

Ramipril; Angiotensin-Converting Enzyme Inhibitors

Condition Hierarchy (Ancestors)

Angina Pectoris; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Eva Prescott, professor

  Sponsor GmbH

  STUDY DIRECTOR

• Marie Michelsen, MD

  Principal Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: August 3, 2015
• First Posted: August 17, 2015
• Study Start: July 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: February 9, 2017

Record last verified: 2017-02

Locations

DK (1)