Percutaneous Coronary Intervention Versus Medical Treatment for Stable Angina Pectoris (DANANGINA)

• ClinicalTrials.gov Identifier: NCT04496648
• Recruitment Status: Recruiting
• First Posted: August 3, 2020
• Last Update Posted: August 3, 2020
• Sponsor: Herlev and Gentofte Hospital
• Information provided by (Responsible Party): Sune Ammentorp Haahr-Pedersen, Herlev and Gentofte Hospital

Study Description

Brief Summary:

Patients with ischemic heart disease and symptoms due to lack of oxygen to the heart on exertion (stable angina pectoris) are usually treated by either percutaneous coronary intervention (PCI) or optimal medical therapy (OMT) alone. In patients with mild to moderate coronary artery disease the prognostic impact of PCI is probably limited. Furthermore it is unclear which treatment is superior in terms of relieving symptoms (PCI or OMT). In this trial, patients with mild to moderate coronary artery disease will be randomized to PCI or sham-PCI. All patients will undergo optimal medical therapy. It is hypothesized that PCI is superior to sham-PCI in patients with stable angina pectoris undergoing optimal medical therapy in terms of symptom-relief.

Condition or disease	Intervention/treatment	Phase
Coronary Heart Disease; Stable Angina; Ischemic Heart Disease	Procedure: Percutaneous Coronary Intervention; Procedure: Sham-percutaneous coronary intervention	Not Applicable

Detailed Description:

Ischemic heart disease (IHD) is a major cause of death and disability worldwide. Patients with ischemic heart disease and symptoms due to lack of oxygen to the heart on exertion (stable angina pectoris) are usually treated by either percutaneous coronary intervention (PCI) or optimal medical therapy (OMT) alone. In patients with mild to moderate coronary artery disease the prognostic impact of PCI is probably limited. Furthermore it is unclear which treatment is superior in terms of relieving symptoms (PCI or OMT). Both treatments are effective in terms of reducing symptoms, but come with potential side effects.

PCI has in previous trials failed to show superiority compared to medical therapy in patients with stable angina pectoris. However, many visually significant lesions do not limit the blood flow significantly to the heart, and stenting such a lesion only exposes the patient to the risk of side effects of intervention. In recent years it has therefore become guideline-recommended practice to perform physiological test to evaluate a potential stenosis. During an angiography this is most often done using fractional flow reserve (FFR).

This study tests the optimal strategy for treatment of angina-symptoms in patients with stable pectoris. PCI is performed with modern stent designs and use of intravascular functional testing (FFR-guided PCI) and compared to sham-PCI.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 450 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized patient-blind sham-controlled trial
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: The Danish Randomized Sham-Controlled Study of Invasive Versus Medical Treatment for Stable Angina Pectoris
• Actual Study Start Date: June 15, 2020
• Estimated Primary Completion Date: May 31, 2022
• Estimated Study Completion Date: September 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Percutaneous Coronary Intervention; Conventional PCI and optimal medical therapy	Procedure: Percutaneous Coronary Intervention; Percutaneous coronary intervention with drug-eluting stents and modern techniques; Other Name: PCI
Placebo Comparator: Sham-percutaneous coronary intervention; Sham-PCI and optimal medical therapy	Procedure: Sham-percutaneous coronary intervention; Sham-PCI procedure for at least 15 minutes that includes shifting the C-arm, reinserting the FFR-wire in the catheter and inflating the device.; Other Name: sham-PCI

Outcome Measures

Primary Outcome Measures :

1. Combined endpoint of strategy success [ Time Frame: 3 months ]
   Number of patients without angina (freedom from angina) and without hospital admission for intolerable stable angina pectoris, unstable angina pectoris, or acute myocardial infarction

Secondary Outcome Measures :

1. Number of all-cause death, any myocardial infarction, stroke, major bleeding, and severe drug reaction [ Time Frame: 3 months ]
   see above
2. Number of conversions to PCI for procedural complication (sham-PCI group) [ Time Frame: 3 months ]
   see above
3. Number of patients with hospital admission for intolerable stable angina, unstable angina pectoris, or acute myocardial infarction [ Time Frame: 3 months ]
   see above
4. Number of patients in CCS class 1, 2, and 3, respectively, without hospital admission for intolerable stable angina, unstable angina pectoris, or acute myocardial infarction [ Time Frame: 3 months ]
   see above
5. Number of patients with clinically driven coronary revascularization [ Time Frame: 3 months ]
   see above
6. Change in CCS class [ Time Frame: 3 months ]
   see above
7. Use of antianginal agents [ Time Frame: 3 months ]
   0, 1, 2, or 3 agents
8. Quality of life score [ Time Frame: 3 months ]
   5- level EQ-5D (EQ-5D-5L) questionnaire. Each dimension will be scored from 0-5 where a higher score means a better outcome. .
9. Change in angina-specific quality of life [ Time Frame: 3 months ]
   Seattle Angina Questionnaire 7. Values will range from 0-100 where higher score means better outcome.
10. Primary composite endpoint in the modified intention-to-treat population [ Time Frame: 3 months ]
    The modified intention-to-treat population is comprised of patients who underwent the study procedure and follow-up without overt or formal unblinding.
11. Change in CCS class in the modified intention-to-treat population [ Time Frame: 3 months ]
    The modified intention-to-treat population is comprised of patients who underwent the study procedure and follow-up without overt or formal unblinding.
12. Change in Seattle Angina Questionnaire 7 score in the modified intention-to-treat population [ Time Frame: 3 months ]
    The modified intention-to-treat population is comprised of patients who underwent the study procedure and follow-up without overt or formal unblinding. Values will range from 0-100 where higher score means better outcome.
13. Change in generic quality of life (EQ-5D-5L) in the modified intention-to-treat population [ Time Frame: 3 months ]
    The modified intention-to-treat population is comprised of patients who underwent the study procedure and follow-up without overt or formal unblinding. Each dimension will be scored from 0-5 where a higher score means a better outcome.

Eligibility Criteria

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

Criteria

Inclusion criteria

• Age 18-85 years
• Patients with stable angina pectoris undergoing elective coronary angiography
• Canadian Cardiovascular Society (CCS) class 2 or 3
• Informed consent
• Lesions in one or more coronary vessels with a diameter >2.5 mm with FFR-values ≤0.80, and suitable for complete revascularization with PCI.

Exclusion criteria

• Contraindication to PCI or dual antiplatelet therapy (DAPT)
• Use of or indication for oral anticoagulants (OAC) or novel oral anticoagulants (NOAC)
• Use of clopidogrel
• Life expectancy of less than 2 years
• Severe valvular disease
• Severe comorbidity
• Acute coronary event within the past 12 months
• Left ventricular ejection fraction ≤35%.
• Renal function with estimated glomerular filtration rate (eGFR) <30 mL/min
• Pregnant or nursing
• Severe coronary artery disease (left main stenosis, 3-vessel disease, proximal left anterior descending stenosis, chronic total occlusion of major vessel)
• Coronary disease where complete revascularization by PCI is considered difficult or impossible.

Contacts and Locations

Contacts

Contact: Sune Ammentorp Haahr-Pedersen, MD; +45 38672267 ext +4530220889; sunped01@regionh.dk

Contact: Niels Thue Olsen, MD, PhD

Locations

Denmark

Gentofte University Hospital; Recruiting

Gentofte, Copenhagen, Denmark, 2900

Contact: Niels Thue Olsen, MD, PhD +45 38 67 25 60 niels.thue.olsen@regionh.dk

Sponsors and Collaborators

Herlev and Gentofte Hospital

Investigators

• Principal Investigator: Ole Havndrup; Zealand Unviersity Hospital
• Principal Investigator: Ole Ahlehoff; Odense University Hospital
• Principal Investigator: Ashkan Eftekhari; Aarhus University Hospital Skejby
• Principal Investigator: Martin Kirk; Aalborg University Hospital
• Principal Investigator: Rikke Sørensen; Rigshospitalet, Denmark

More Information

• Responsible Party: Sune Ammentorp Haahr-Pedersen, Primary Investigator, Herlev and Gentofte Hospital
• ClinicalTrials.gov Identifier: NCT04496648
• Other Study ID Numbers: H-18009651
• First Posted: August 3, 2020
• Last Update Posted: August 3, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data will be shared upon request.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: 1 year after publication
• Access Criteria: Upon request

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sune Ammentorp Haahr-Pedersen, Herlev and Gentofte Hospital:

Atherosclerosis; Fractional flow reserve; Optimal medical therapy; Antianginal; Percutaneous Coronary Intervention

Additional relevant MeSH terms:

Heart Diseases; Angina Pectoris; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Angina, Stable; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Arteriosclerosis; Arterial Occlusive Diseases