Microvascular Dysfunction in Patients With Long-Covid Syndrome and Angina

NCT07559994 | Active Not Recruiting DMC

• 1 other identifier: PI21/01481
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

Long-Covid INOCA is an investigator-initiated, prospective, randomized, sham-controlled, single center study. Its objective is to investigate the benefits of tailored medical therapy according to the results of the coronary functional testing (CFT) against the routine standard of care and the prevalence and type of ischemia with non-obstructive coronary arteries (INOCA) in patients with LCS and chest pain. All LCS patient with new onset of chest pain will be enrolled. Invasive coronary angiogram and epicardial physiological assessment will be performed to exclude significant epicardial coronary artery disease. Patients without significant epicardial coronary disease will undergo CFT which include Acetylcholine test and Coronary microvascular function test. Patients will be randomized into 2 groups: 1) tailored treatment group guided by the results of CFT (intervention) and 2) the routine standard of care group (sham). All patients will undergo the angina symptom and the quality-of-life (QoL) assessment at baseline, 3, 6, and 12 months using the Seattle Questionnaire of Angina (SAQ). In the sham group, patients and physicians will be blinded to the results of coronary functional testing for 3 months. Treatment of INOCA will be provided in both groups. The main hypothesis of the Long-Covid INOCA study states that, in LCS patients with chest pain, treatment guided by CFT will demonstrate better angina symptom control and improvement in quality of life (QoL) comparing to the routine standard of care.

Conditions

Long COVID; Angina (Stable); Chronic Coronary Syndrome; INOCA (Ischemia With Non Obstructive Coronary Artery Disease)

Keywords

Long covid; Chest pain; Ischemia with non obstructive coronary artery disease

Outcome Measures

Primary Outcomes (1)

• The changes in angina symptom and quality of life assessed by Seattle Questionnaire of Angina score in the treatment guided group comparing to the standard of care group

  The Seattle Angina Questionnaire (SAQ) measures 5 dimensions of coronary artery disease (physical limit, stability, frequency, satisfaction, disease perception) on a 0-100 scale, where higher scores indicate better health status. Scores are interpreted as: 0-24 (Poor), 25-49 (Fair), 50-74 (Good), 75-100 (Excellent).

  From the date of enrollment to the end of follow up period at 12 months

Secondary Outcomes (1)

• The prevalence and type of INOCA in LCS patients with chest pain

  From the date of enrollment to the last follow up period at 12 months

Study Arms (2)

Intervention

ACTIVE COMPARATOR

Treatment of INOCA guided by the results of the coronary functional testing during the entire follow up period (12 months)

Diagnostic Test: Coronary functional test

Sham

SHAM COMPARATOR

Treatment of INOCA by the routine standard of care for the first 3 months and guided by the results of the coronary functional testing during the rest of the follow up period (9 months)

Diagnostic Test: Coronary functional test

Interventions

Coronary functional test DIAGNOSTIC_TEST

CFT will be reported as follow: 1) normal coronary functional testing 2) vasomotor disorder (including both epicardial and microvascular) 3) coronary microvascular dysfunction (including both structural and functional) and 4) combined vasomotor disorder and coronary microvascular dysfunction.

Intervention; Sham

Eligibility Criteria

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

You may qualify if:

• \- All patients with the history of SARS-CoV-2 infection, either with acute infection confirmed by PCR or antigen testing, or with past infection demonstrated by serological testing, with symptoms suggestive of LCS such as post exertional malaise, persistent fatigue, difficulty concentrating or shortness of breath who present with typical angina or angina equivalent chest pain starting after SARS-CoV2 infection

You may not qualify if:

• Previously been diagnosed with coronary artery disease
• Severe left ventricular systolic dysfunction (LVEF) \< 30%
• Any moderate to severe concomitant structural heart disease (e.g. moderate to severe valvular heart abnormalities, severe left ventricular hypertrophy)
• Severely reduced renal function (glomerular filtration rate \< 30 ml/min/1.73m2)
• Contraindications to the administration of Adenosine or Acetylcholine
• A life expectancy of less than 2 years

Sponsors & Collaborators

• Fundacion Investigacion Interhospitalaria Cardiovascular: lead

Study Sites (1)

Hospital Clinico San Carlos

Madrid, Madrid, 28005, Spain

Location

Related Publications (6)

• Carfi A, Bernabei R, Landi F; Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.2020.12603.

  PMID: 32644129 BACKGROUND

• The Lancet. Facing up to long COVID. Lancet. 2020 Dec 12;396(10266):1861. doi: 10.1016/S0140-6736(20)32662-3. No abstract available.

  PMID: 33308453 BACKGROUND

• Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 May 2;395(10234):1417-1418. doi: 10.1016/S0140-6736(20)30937-5. Epub 2020 Apr 21. No abstract available.

  PMID: 32325026 BACKGROUND

• Kunadian V, Chieffo A, Camici PG, Berry C, Escaned J, Maas AHEM, Prescott E, Karam N, Appelman Y, Fraccaro C, Louise Buchanan G, Manzo-Silberman S, Al-Lamee R, Regar E, Lansky A, Abbott JD, Badimon L, Duncker DJ, Mehran R, Capodanno D, Baumbach A. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. Eur Heart J. 2020 Oct 1;41(37):3504-3520. doi: 10.1093/eurheartj/ehaa503.

  PMID: 32626906 BACKGROUND

• Ahmed AI, Saad JM, Han Y, Alahdab F, Malahfji M, Nabi F, Mahmarian JJ, Cooke JP, Zoghbi WA, Al-Mallah MH. Coronary Microvascular Health in Patients With Prior COVID-19 Infection. JACC Cardiovasc Imaging. 2022 Dec;15(12):2153-2155. doi: 10.1016/j.jcmg.2022.07.006. Epub 2022 Aug 17. No abstract available.

  PMID: 36481086 BACKGROUND

• Ford TJ, Stanley B, Sidik N, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, McCartney P, Corcoran D, Collison D, Rush C, Sattar N, McConnachie A, Touyz RM, Oldroyd KG, Berry C. 1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA). JACC Cardiovasc Interv. 2020 Jan 13;13(1):33-45. doi: 10.1016/j.jcin.2019.11.001. Epub 2019 Nov 11.

  PMID: 31709984 BACKGROUND

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Angina, Stable; Chest Pain

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Angina Pectoris; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Javier Escaned Barbosa, MD, PhD

Model Details: INOCA treatment guided by the results of coronary functional test

Study Record Dates

• First Submitted: April 28, 2026
• First Posted: April 30, 2026
• Study Start: September 2, 2021
• Primary Completion: April 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

ES (1)