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

The Danish Randomized Sham-Controlled Study of Invasive Versus Medical Treatment for Stable Angina Pectoris

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.

Study Overview

• Status: Unknown
• Conditions: Coronary Heart Disease; Ischemic Heart Disease; Stable Angina
• Intervention / Treatment: Procedure: Percutaneous Coronary Intervention; Procedure: Sham-percutaneous coronary intervention

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 Type: Interventional
• Enrollment (Anticipated): 450
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen
    • Gentofte, Copenhagen, Denmark, 2900
      • Recruiting
      • Gentofte University Hospital
      • Contact: Niels Thue Olsen, MD, PhD; Phone Number: +45 38 67 25 60; Email: niels.thue.olsen@regionh.dk

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: sham-PCI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combined endpoint of strategy success	Number of patients without angina (freedom from angina) and without hospital admission for intolerable stable angina pectoris, unstable angina pectoris, or acute myocardial infarction	3 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: 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

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Anticipated): May 31, 2022
• Study Completion (Anticipated): September 30, 2022

Study Registration Dates

• First Submitted: June 15, 2020
• First Submitted That Met QC Criteria: July 29, 2020
• First Posted (Actual): August 3, 2020

Study Record Updates

• Last Update Posted (Actual): August 3, 2020
• Last Update Submitted That Met QC Criteria: July 29, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Percutaneous Coronary Intervention; Atherosclerosis; Fractional flow reserve; Optimal medical therapy; Antianginal
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Chest Pain; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Angina Pectoris; Angina, Stable
• Other Study ID Numbers: H-18009651

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared upon request.
• IPD Sharing Time Frame: 1 year after publication
• IPD Sharing Access Criteria: Upon request
• 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