A double-blind randomised placebo-controlled trial of percutaneous coronary intervention for the relief of stable angina without antianginal medications: design and rationale of the ORBITA-2 trial
Alexandra Nowbar Nowbar, Christopher Rajkumar, Michael Foley, Fiyyaz Ahmed-Jushuf, James Howard Howard, Henry Seligman, Ricardo Petraco, Sayan Sen, Sukhjinder Nijjer Nijjer, Matthew Shun-Shin Shun-Shin, Thomas Keeble Keeble, Afzal Sohaib, David Collier, Patrick McVeigh, Frank Harrell Harrell, Darrel Francis Francis, Rasha Al-Lamee Al-Lamee
Abstract
Percutaneous coronary intervention (PCI) is frequently performed for stable angina. However, the first blinded trial, ORBITA, did not show a placebo-controlled increment in exercise time in patients with single-vessel disease, at 6 weeks, on maximal antianginal therapy. ORBITA-2 will assess the placebo-controlled efficacy of PCI on angina frequency in patients with single- or multivessel disease, at 12 weeks, on no antianginal therapy. ORBITA-2 is a double-blind placebo-controlled trial randomising participants with (i) angina at presentation, (ii) documented angina during the 2-week pre-randomisation symptom assessment phase, (iii) objective evidence of ischaemia, (iv) single- or multivessel disease, and (v) clinical eligibility for PCI. At enrolment, antianginals will be stopped, and angina questionnaires completed. Participants will record their symptoms on a smartphone application daily throughout the trial and will undergo exercise treadmill testing and stress echocardiography at pre-randomisation. They will then undergo coronary angiography with unblinded invasive physiology assessment. Eligible participants will then be sedated to a deep level of conscious sedation and randomised 1:1 between PCI and placebo. After the 12-week blinded follow-up period, they will return for questionnaires, exercise testing and stress echocardiography assessment. If angina becomes intolerable, antianginals will be introduced using a prespecified medication protocol. The primary outcome is an angina symptom score using an ordinal clinical outcome scale for angina. Secondary outcomes include exercise treadmill time, angina frequency, angina severity and quality of life. Trial registration: ClinicalTrials.gov: NCT03742050.