The PIONEER IV trial (NCT04923191) is a prospective, all-comers, multi-centre trial, planned to randomize 2,540 patients in a 1:1 ratio to percutaneous coronary intervention (PCI) guided by angiography-derived physiology or usual care with unrestricted use in both arms of the Healing-Targeted Supreme sirolimus-eluting stent (HT Supreme, SINOMED, Tianjin, China). Patients with at least 1 significant lesion (diameter stenosis ≥50% by visual assessment) for PCI were included. The primary endpoint is a noninferiority comparison of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, any myocardial infarction, or any clinically and physiologically driven revascularization at 1 year.
At the initiation of the trial, angiography-derived physiology analysis was performed using the CE-marked QAngio XA 3D/ quantitative flow ratio (QFR) software (Medis Medical Imaging Systems B.V., Leiden, the Netherlands). However, to facilitate the recruitment at centres where the RainMed system was already in use, especially in France, the study protocol was amended to allow the inclusion of the RainMed system. The computational pressure–flow dynamics–derived fractional flow reserve (caFFR) (RainMed Ltd, Suzhou, China) is another well-validated alternative to conventional wire-based fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR), which has obtained CE marking for clinical use. caFFR was first validated in 323 patients of the FLASH FFR study which showed the diagnostic accuracy of 95.7% as compared with invasive FFR. The head-to-head comparison by an independent core-lab demonstrated that the diagnostic accuracy of caFFR and Medis QFR system for predicting a pressure-derived FFR ≤0.80 was comparable with a higher discrimination compared to 2-dimensional quantitative coronary angiography percent diameter stenosis (2D-QCA %DS) in a prospective cohort. In July 2023, the study protocol was amended to add caFFR as alternative angiography-derived physiology analysis ( Table 1 ).
Table 1
Summary of study protocol amendment
| Original protocol | Amended protocol | |
|---|---|---|
| Angiography-derived physiology analysis | • QFR | • QFR and caFFR |
| Sample size | • 2,540 | • 2,130 |
| Power | • 90% | • 85% to account for alpha spending associated with a prespecified interim analysis. |
| Interim analysis | • Not planned |
• Planned at a 60% information fraction (1,270/2,130) using a Lan–DeMets Pocock-type alpha spending function with a one-sided p-value threshold of 0.035.
• Noninferiority at the final analysis (100% information fraction) will be declared at P < 0.0279. |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
