MICRO: a Registry Study in Patients With Microvascular Angina (MICRO)

A Multicenter Registry on the Diagnosis of Patients With Chronic Angina and no Angiographic Coronary Artery Stenosis

The evidence above demonstrates that microvascular dysfunction is an important determinant of patient prognosis, which however remains poorly classified. Given the high burden of disease and the severity of the functional impairment in these patients, the lack of a clear definition for this disease has a potentially large clinical importance. It is important to better describe the phenotype of these patients, identify the predictors of prognosis, and determine the impact of diagnosis.

Study Overview

• Status: Recruiting
• Conditions: Microvascular Disease
• Intervention / Treatment: Device: Assessment of microvascular function with intracoronary hemodilution

Detailed Description

The study is designed as prospective registry. Patients with angina CCS II-IV undergoing assessment of microvascular function will be enrolled.

The study does not interfere with the medical standards at the sites with regards to patient treatment or follow-up care.

Study duration and schedule The duration of this study is expected to be 7 years. The subject recruitment is planned to start in January 2020 and end in January 2022. The actual overall study duration or subject recruitment period may differ from these time periods. Per-patient, the duration of participation will be up to 5 years. Patients will be evaluated at hospital discharge, at 12 months and 5 years (the latter two as telephone contacts).

Number of subjects and study centers It is planned to enroll 1000 subjects in the registry based on power calculations as described. Recruitment and treatment of subjects is expected to be performed in 10 study centers.

Primary endpoint The primary endpoint is the composite of cardiovascular death, myocardial infarction, rehospitalization for angina or heart failure, and unplanned coronary angiography at 12 months.

Secondary endpoints Each of the components of the primary endpoint Seattle Angina Questionnaire SAQ-7 Physical limitation scale SAQ-7 angina stability scale SAQ-7 angina frequency scale SAQ-7 angina quality of life EQ-5D-5L Beck depression inventory

The SAQ-7 "angina frequency" domain has been shown to correlate to improvements in microvascular function in the WISE study. SAQ-7-7 has been also used in a number of studies, including the ISCHEMIA study.

Other patient questionnaires are also standardized tests for the assessment of quality of life, depression and symptom severity in coronary artery disease studies.

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Tommaso Gori, Dott med, PhD; Phone Number: 2829 +496131 17; Email: tommaso.gori@unimedizin-mainz.de

Study Locations

• Germany
  • RLP
    • Mainz, RLP, Germany, 55131
      • Recruiting
      • Universitätsmedizin Mainz
      • Contact: Tommaso Gori, Dtt med, PhD; Phone Number: 06131176903; Email: tommaso.gori@unimedizin-mainz.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with angina without apparent obstructive coronary artery disease (no coronary stenosis >75% at angiography) undergoing clinically-indicated assessment of coronary microvascular function.

Description

Inclusion Criteria:

• Age ≥ 18 and <85 years.
• Chronic coronary syndrome (including patients with anginal equivalents)
• Angina CCS class II-IV
• Evidence of reversible ischemia on non-invasive testing

• Availability of the following measurements:

  1. Index of microvascular resistances (IMR),
  2. Resting full-cycle ratio (RFR),
  3. Fractional flow reserve (FFR),
  4. Coronary flow reserve (CFR)
• Willingness to participate and ability to understand read and signed the informed consent document before the procedure

Exclusion Criteria:

At least one of the following:

• Pregnancy and or lactation.
• Medical or psychological conditions that would jeopardize an adequate and orderly participation.
• Left ventricular ejection fraction lower than 30%
• Previous coronary artery bypass surgery (CABG) to all major branches in the LAD and left circumflex (LCX) territory, such that IMR cannot be measured
• Decompensated congestive heart failure (CHF)
• Chronic or acute renal failure with creatinine >2mg/dl
• Severe valvular heart disease
• Patients with comorbidities limiting life expectancy to less than one year

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients undergoing coronary microvascular function assessment	Device: Assessment of microvascular function with intracoronary hemodilution; The pressure/temperature wire allows assessing coronary flow reserve, intracoronary pressure, and coronary flow to calculate multiple parameters of coronary macro- and microvascular function.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic impact of resting resistances	The impact of resting resistances (expressed as Mean Transit Time, i.e. time for a saline bolus to reach the wire thermistor times distal pressure) on the incidence of patient-oriented outcomes (composite of cardiovascular death, myocardial infarction, rehospitalization for angina or heart failure and unplanned coronary angiography) at 12 months	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between SAQ measures and IMR	Correlation of IMR with Seattle Angina Questionnaire, including each of its components (SAQ-7 Physical limitation scale, SAQ-7 angina stability scale, SAQ-7 angina frequency scale, SAQ-7 angina quality of life) at 6 months, 1 year and yearly to 5 years	6 months, 1 year and yearly to 5 years.
Correlation between depression and IMR	Correlation of IMR with Beck depression inventory scores	6 months, 1 year and yearly to 5 years.
Correlation between physical ability and IMR	Correlation of IMR with parameters of 5-EQ-EL	6 months, 1 year and yearly to 5 years.
Distribution of mean transit time (Tmn)	Distribution of Tmn (seconds).	At inclusion
Distribution of index of microvascular resistances (IMR)	Distribution of IMR, units.	At inclusion
Distribution of aortic and distal pressure	Distribution of Pa (aortic pressure) and Pd (distal arterial pressure) in mmHg.	At inclusion

Collaborators and Investigators

• Sponsor: Johannes Gutenberg University Mainz

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2020
• Primary Completion (Anticipated): October 10, 2024
• Study Completion (Anticipated): October 10, 2029

Study Registration Dates

• First Submitted: October 10, 2020
• First Submitted That Met QC Criteria: October 27, 2020
• First Posted (Actual): November 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 29, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Coronary artery disease; Angina
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris
• Other Study ID Numbers: 2020-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No