A Partially Randomized Patient Preference Trial to Assess the Quality of Life and Patency Rate After Minimally Invasive Cardiac Surgery-Coronary Artery Bypass Grafting: the MICS-CABG PRPP Trial
Phase: NA
Conditions: Minimally Invasive Cardiac Surgery
Sponsor: Peking University Third Hospital

Study Protocol and Statistical Analysis Plan
Study Protocol
Background: Minimally invasive cardiac surgery-coronary artery bypass grafting (MICS-CABG)
has emerged as a safe alternative to standard cardiac surgery. However, treatment preferences can
decrease the generalizability of RCT results to the clinical population (i.e., reduce external validity)
and influence adherence to the treatment protocol and study outcomes (i.e., reduce internal
validity). However, this has not yet been properly investigated in randomized trials with
consideration of treatment preferences.
Study Design: In this study, patients with a preference will be allocated to treatment strategies
accordingly, whereas only those patients without a distinct preference will be randomized. The
randomized trial is a 248-patient controlled, randomized, investigator-blinded trial. It is designed
to compare whether treatment with MICS-CABG is beneficial in comparison to CABG. This
study is aimed to establish the superiority hypothesis for the physical component summary (PCS)
accompanied by the non-inferiority hypothesis for overall graft patency. Patients with no treatment
preference will be randomized in a 1:1 fashion to one of the two treatment arms.
The primary efficacy endpoints are the PCS score at 30 days after surgery and the overall patency
rate of the grafts within 14 days after surgery. Secondary outcome measures include the PCS score
and patency rate at different time points. Safety endpoints include major adverse cardiac and
cerebrovascular events, complications, bleeding, wound infection, death, etc.
Conclusions: This trial will address essential questions of the efficacy and safety of MICS-CABG.
The study will also address the impact of patients’ preferences on external validity and internal
validity.
Statistical Analysis Plan
Statistical analyses will be performed using IBM SPSS Statistics for Windows, version 26.0 (IBM
Corp., Armonk, N.Y., USA). First, a descriptive analysis will be conducted. Normally distributed
continuous variables will be expressed as the mean and standard deviation, and nonnormally
distributed continuous variables will be expressed as the median and interquartile range (IQR).
Categorical variables will be expressed as percentages.
The primary efficacy endpoint will be assessed in the per protocol population and the
intention-to-treat (ITT) population. Statistical significance is needed for both primary endpoints.
Therefore, no formal adjustment of the significance level of the elementary hypothesis tests is
necessary. For the primary efficacy endpoint PCS at one month after surgery, the superiority of
MICS-CABG to OPCABG could be claimed if the lower limit of the 95% CI (for the difference in
progression-free survival [PFS] between groups) is greater than 2. For the other coprimary
efficacy endpoint, namely, the overall patency rate at two weeks after surgery, non-inferiority of
MICS-CABG to OPCABG could be claimed if the lower limit of the 95% CI (for the difference in
patency rate between groups) is greater than −6%.
To explore the impact of patients’ preference on external validity, the participation rate and the
randomization refusal rate will be analyzed. The differences in baseline characteristics between
the random cohort and the preference cohort will be compared to assess if a specific patient group
has accepted randomization. To explore the impact of patients’ preference on internal validity, the
proportion of patients lost to follow-up will be analyzed. To explore the impact of patients’
preference on primary outcomes, we will examine treatment-specific differences between the

preference and randomization groups. In addition, we will make comparisons (1) between
randomized MICS-CABG and preference MICS-CABG and (2) between randomized sternotomy
CABG and preference sternotomy CABG to explore the impact of preference on outcome
assessment.
The chi-squared test will be used to examine the differences in binary secondary outcomes (e.g.,
graft patency rate at different time points and secondary surgery). Kaplan-Meier survival analysis
will be employed for timed endpoints such as MACCE. The t test and Mann–Whitney U test will
be used to examine the differences in continuous secondary outcomes (e.g., SF-36 at different time
points, mechanical ventilation time, hospitalization costs and postoperative hospital stay). The
level of significance is set at α =0.05.