RECOVER with INOCA: a Study of a Cardiac Rehabilitation Program in Patients with Ischemia with Nonobstructive Coronary Artery Disease (INOCA)

RECOVER with INOCA: a Randomized, Prospective Study of a Cardiac Rehabilitation Program in Patients with Ischemia with Nonobstructive Coronary Artery Disease (INOCA)

The goal of this clinical trial is to learn if a cardiac rehabilitation program (CRP) improves functional capacity in adults with INOCA (ischemia with non obstructive coronary arteries). The main questions it aims to answer are:

• Does CRP improves maximal functional capacity (measured by VO2peak) in INOCA patients?
• Does CRP improve as well quality of life, adherence to Mediterranean diet, emotional state, functional independence angina episodes and sleep quality?

Researchers will compare CRP (treatment group) to standard recommendations (control group) to see if CRP works better for INOCA patients

Participants will:

Take part of CRP or standard recommendations for 3 months Visit the clinic in the beginning and in the end of the study for checkups and tests

Study Overview

• Status: Completed
• Conditions: INOCA (ischemia with Non Obstructive Coronary Artery Disease)
• Intervention / Treatment: Other: Standard recommendations; Other: Telematic cardiac rehabilitation program, that includes exercise, educational and psychological sessions during 3 months

Detailed Description

A prospective, single-centre, randomized study with patients diagnosed with INOCA to assess their participation in a 3-month telehealth-based holistic cardiac rehabilitation program (CRP). Exclusion criteria were based on contraindications for participating in the telehealth CRP: alarm signs in the stress test (ventricular arrhythmias, hypotensive response, ST segment changes, or symptoms of ischemia), left ventricular ejection fraction (LVEF) <40%, or presence of pacemakers/defibrillators. Additionally, patients without a mobile device/tablet/computer with internet access to connect to exercise and educational sessions were excluded. Finally, participants should be stable in terms of angina episodes, defined as the absence of hospitalizations or decompensations in the number of angina episodes, as well as no changes in antianginal medications for 3 months prior to inclusion.

The primary endpoint is the improvement in functional capacity, objectively measured by the change in peak oxygen consumption (VO2peak) obtained from cardiopulmonary exercise testing (CPET) after 3 months of CRP (treatment group), compared to standard recommendations (control group). Secondary endpoints are CRP impact on quality of life, adherence to Mediterranean diet, emotional state, functional independence, angina episodes and sleep quality. The investigators selected pure VSA and pure MCA endotypes for the inclusion, to avoid confusion factors and to see if there were different results between both endotypes. A sample of 24 patients was selected to detect a 4.5 ml/kg/min difference in VO2peak.

The study scheme is as follows:

1. Recruitment: INOCA patients (confirmed diagnosis with microcirculation and provocation testing) are referred from ischemic heart disease consultations.

2. Initial Assessment Visit:

   • Part 1: Cardiologist and hemodynamic nurse explain the project, and if the patient agrees to participate, randomization (CRP yes or no) occur, and informed consent is signed. Blood samples are taken for initial assessment (basic profile, haemostasis, lipid profile, and HbA1c). Additionally, scales for quality of life (EuroQol), anxiety and depression (HADS), Mediterranean diet (PREDIMED), weekly exercise volume (IPAQ), functional (Barthel), and angina (SAQ-7) assessments are completed.
   • Part 2: Assessment in the cardiac rehabilitation clinic and initial CPET (cardiopulmonary stress test) testing for all patients. If the patient belongs to the CRP group, an individualized exercise prescription is made for the physiotherapist. If not, general exercise recommendations are provided. In both cases, a final CPET visit is scheduled at 3 months.
3. Cardiac Rehabilitation Program (3-month duration, for the intervention group): 2 individualized exercise sessions per week (via Teams platform) with the physiotherapist, 1 educational session per week via Teams with nursing, and 1 educational session per week via Teams with psychology.
4. Final Visit in Cardiac Rehabilitation: Scales wee reassessed, CPET is conducted, and a final medical assessment is performed. A final blood test and nursing assessment is also conducted, including an ad hoc patient experience survey regarding the program. A final medical report with their evolution and recommendations for follow up is given to all patients.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Villarroel 170

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• All men or women >18 years old with cath lab diagnosis of INOCA of 2 possible endotypes: vasoespasm or microvascular disease.
• All participants must have a mobile device/tablet/computer with internet access to connect to exercise and educational sessions
• Participants should be stable in terms of angina episodes, defined as the absence of hospitalizations or decompensations in the number of angina episodes, as well as no changes in antianginal medications for 3 months prior to inclusion.

Exclusion Criteria:

• Alarm signs in the stress test (ventricular arrhythmias, hypotensive response, ST segment changes, or symptoms of ischemia)
• Left ventricular ejection fraction (LVEF) <40%, or presence of pacemakers/defibrillators

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: Cardiac rehabilitation group (treatment group); 3-mont telematic cardiac rehabilitation program for 3 months, including exercise, educational and psychological sessions	Other: Telematic cardiac rehabilitation program, that includes exercise, educational and psychological sessions during 3 months; 2 group and telematic exercise sessions/week, 1 educational session/week and 1 psychological session/week, during 3 months. There are no drugs or devices involved in the intervention.
Active Comparator: Standard recommendations (control group); Standard recommendations about exercise, education and psychological advise for INOCA patients	Other: Standard recommendations; Standard recommendations about exercise, educational and psychologicla advice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal functional capacity	Change in VO2peak measured with CPET (cardiopulmonary stress test)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Angina episodes	Change in the number of angina episodes/month	3 months
EuroQol (EQ-5D)	Full name: EuroQol Five-Dimension Scale; Purpose: Measures health-related quality of life (HRQoL) across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. It also includes a visual analogue scale (VAS) for self-rated health.; Minimum value: 0 (equivalent to death) or negative values (worse than death, depending on country-specific value sets); Maximum value: 1 (perfect health); Interpretation: Higher scores indicate a better health-related quality of life.	3 months
PREDIMED	Full name: PREDIMED Mediterranean Diet Adherence Screener; Purpose: Assesses adherence to the Mediterranean diet, which is associated with reduced cardiovascular risk and improved health outcomes.; Minimum value: 0 (no adherence); Maximum value: 14 (maximum adherence); Interpretation: Higher scores indicate a better outcome, meaning greater adherence to the Mediterranean diet and its associated health benefits. A score ≥9 suggests high adherence.	3 months
HADS	Full name: Hospital Anxiety and Depression Scale - Depression (HADS-D) and Anxiety (HADS-A) Subscales; Purpose: Assesses symptoms of anxiety (HADS-A) and depression (HADS-D) in hospital and primary care settings, avoiding somatic symptoms to focus on emotional distress.; Minimum value: 0 (no symptoms); Maximum value: 21 per subscale (total 42 if both are combined); Interpretation: Higher scores indicate a worse outcome, meaning more severe anxiety or depression symptoms. Scores of 8-10 suggest mild symptoms, 11-14 moderate, and ≥15 severe symptoms.	3 months
Barthel Score	Full name: Barthel Index of Activities of Daily Living; Purpose: Evaluates functional independence in activities of daily living (ADLs), such as bathing, dressing, mobility, and feeding, primarily in stroke and rehabilitation patients.; Minimum value: 0 (total dependence); Maximum value: 100 (complete independence); Interpretation: Higher scores indicate a better outcome, meaning greater independence in daily activities.	3 months
PSQI	Full name: Pittsburgh Sleep Quality Index; Purpose: Assesses sleep quality and disturbances over a 1-month period. It consists of 7 components: Subjective sleep quality, Sleep latency, Sleep duration, Habitual sleep efficiency, Sleep disturbances, Use of sleep medication, Daytime dysfunction; Minimum value: 0 (best sleep quality); Maximum value: 21 (worst sleep quality); Interpretation: Higher scores indicate a worse outcome, meaning poorer sleep quality. A global PSQI score >5 suggests poor sleep quality.	3 months

Collaborators and Investigators

• Sponsor: Hospital Clinic of Barcelona
• Collaborators: Societat Catalana de Cardiologia
• Investigators: Principal Investigator: Margarita Calvo-Lopez, MD, Hospital Clinic of Barcelona

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Actual): December 15, 2024
• Study Completion (Actual): December 15, 2024

Study Registration Dates

• First Submitted: March 14, 2025
• First Submitted That Met QC Criteria: March 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Cardiac rehabilitation; INOCA; Functional capacity
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Ischemia; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: HCB/2024/0926

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD collected throughout the trial
• IPD Sharing Time Frame: Beginning 3 months and ending 1 year after the publication of results

IPD Sharing Access Criteria

Access to IPD and supporting information will be granted to qualified researchers, healthcare professionals, and regulatory authorities for scientific, clinical, or public health purposes. Requests will be reviewed by an independent data access committee to ensure compliance with ethical and legal requirements.

Available Data: De-identified IPD, study protocol, statistical analysis plan, informed consent form template, and study results summary.

Access Mechanism: Applicants must submit a research proposal, sign a data use agreement (DUA), obtain committee approval, and access data via a secure platform.

Ethical and Legal Compliance: Access will follow GDPR, HIPAA, and ethical guidelines, ensuring de-identification and restricted use for approved research purposes.

Data Availability: Data will be accessible for at least five years post-publication, with potential extensions.

Contact: For access requests, contact margacal1912@gmail.com

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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