Study population and randomisation
We conducted a single-centre, double-blinded, randomised controlled trial with an allocation ration of 1:1.
All patients admitted to University and Hospital Fribourg for an elective invasive coronary procedure (diagnostic coronary angiography and/or percutaneous coronary intervention) aged over 18 years were eligible for inclusion. Patients having already contacted a “Secret Maker” to speak the formula on their behalf prior to the coronary angiography and those unable or unwilling to provide written informed consent and/or to participate in clinical follow-up were excluded. Patients with a major procedural complication (anaphylaxis, stroke, periprocedural myocardial infarction, pulmonary embolism, death) were likewise excluded.
Baseline patient and procedural characteristics were collected by dedicated study nurses during the index hospitalisation for elective coronary angiography. Clinical outcome was collected at discharge.
All patients underwent coronary angiography via the radial and/or femoral artery. Coronary angiography was performed according to good clinical practice using 5 F or 6 F diagnostic catheters at the operator’s discretion. Treatment modalities including devices used during percutaneous coronary intervention and antithrombotic management were at the physician’s discretion and according to the local standard of care at the time of the intervention.
A research nurse randomly assigned patients on the day of the intervention using sealed envelopes. Patients were randomised to receive standard care (C-group) or to receive standard care and “The Secret” (S-group).
The patients, cardiologists and nurses assessing bleeding outcomes were unaware of the patient’s group or the identity of the “Secret Maker”. Bleeding outcomes were classified and adjudicated internally by an event adjudication committee.
For the intervention group we asked “Secret Makers” to give the formula after study inclusion but prior to coronary angiography. The “Secret Makers”, 15 men and woman from an official list,6 agreed to participate in the study and were randomly selected on the same day from that list. The full name and birthday of the respective patient in the intervention group was communicated bytelephone to the Secret Maker, who then performed the blood charm sometime between study inclusion and coronary angiography. The exact wording of the charm to staunch bleeding was unknown to the investigators and might have differed from one “Secret Maker” to another.
All factors that could affect bleedings outcomes before, during and after the procedure were collected the day of the intervention and then compared by group. We also considered patients with high bleeding risk (HBR) depending on the definition of Academic Research Consortium High Bleeding Risk (ARC-HBR). Major and minor criteria are described by Urban et al.7 Patients were at HBR if at least one major or two minor criteria were met.
Clinical endpoints
The primary outcome was the rate of in-hospital bleeding according to the Bleeding Academic Research Consortium (BARC) consensus definition.8
The null hypothesis was that there is no difference in bleeding rate between the two groups, and the alternative hypothesis was that there was a significant difference in bleeding rate in one of the two groups. The study complied with the Helsinki Declaration and was approved by the local ethics committee (CER-VD 2021–01877). All patients provided written informed consent.
Statistical analysis
Categorical variables were reported as counts and percentages; continuous variables were reported as means and standard deviations. Normality was assessed by the computation of Q-Q plots and the Shapiro–Wilk test. Continuous variables were analysed using the Student’s t-test or the Wilcoxon rank-sum test per distribution. Categorical variables were compared using chi-square or Fisher exact test as appropriate. All statistical analyses were performed using dedicated software (StataCorp LP, College Station, Texas) at a two-tailed significance level of alpha=0.05.