Statistical analysis
No formal sample size calculation was performed due to no relevant data available from previous trials. For this exploratory trial, the sample size (50 patients per group) was based on the recommendation of the Steering Committee. Statistical analyses were performed on a modified intention-to-treat (mITT) principle, which comprised of patients who are randomized, regardless of whether they prematurely discontinue treatment or are otherwise protocol violators/deviators. Participants who lost to follow-up or withdrew will not be included in the mITT population. Baseline characteristics and procedural details were compared with Student’s This trial of HOPES2 was registered with ClinicalTrials.gov with the number NCT03744533 on November 16, 2018, and is now closed at all participating sites.