The prophylactic effect of oral Melatonin on cardiac and inflammatory biomarkers after Artery Bypass Grafting Surgery (CABG) on pump technique

The prophylactic effect of oral Melatonin on cardiac and inflammatory niomarkers after Artery Bypass Grafting (CABG) surgery on pump technique

Clinical trial with control group, Parallel group, Double blinded, randomized phase 3 with 74 patients, Randomization using permuted blocks

Patients undergoing coronary artery bypass graft surgery at Shahid Mohammadi Hospital in Bandar Abbas will be enrolled in the study and will be randomly allocated to the intervention and control groups using a permuted-block randomization method. The participants and the data analyst will be blinded (double-blind).

Inclusion criteria: Patients who are candidates for elective coronary artery bypass surgery, age 30 to 80 years, anesthesia class 2 and 3, not receiving analgesics within 6 hours before surgery, and cardiac ejection fraction greater than 40 percentage. Exclusion criteria: Unwillingness to participate in the research project.

Patients in the intervention group receive oral melatonin tablets (3 mg, Razak Company, Iran) 12 hours before surgery and on the morning of surgery. All patients are evaluated for anesthesia one day before surgery, after arrival in the operating room undergo standard monitoring, and their baseline hemodynamic parameters are recorded. Patients in the control group receive oral placebo tablets (3 mg, Dara Kimia Aria Company, Iran) 12 hours before surgery and on the morning of surgery.

C‑Reactive Protein; Erythrocyte Sedimentation Rate; Cardiac Troponin; Creatine Kinase–Myocardial Band; Systolic Blood Pressure; Diastolic Blood Pressure; Mean Arterial Pressure; Lactate Dehydrogenase; Interleukin‑6

The study employs a permuted block randomization method. To this end, two treatment groups, A and B, were defined as AB and BA blocks. Random numbers were generated within the range of 0 to 9, where numbers 0–4 were assigned to the AB block, and 5–9 were assigned to the BA block. Upon selecting a random number from the table, if the number falls within 0–4, the AB block is assigned; consequently, the next two participants are enrolled, with the first receiving treatment A and the second receiving treatment B. This procedure is repeated systematically to assign treatment groups for subsequent participants. Although this method ensures an equal number of observations in both groups, the small block size poses a risk of treatment allocation predictability by the investigator. To mitigate this, the randomization list is generated prior to the commencement of the study by an independent, blinded individual who is not involved in the clinical care of the participants.

In this double-blind clinical trial, in order to maintain blinding, capsules containing melatonin and placebo before the start of the study were prepared by an independent person outside the research team in identical packages in terms of shape, color, and label and were randomly labeled with codes A and B. The coding key is kept only by this independent person and remains confidential until the completion of statistical analysis and finalization of the results. Allocation of participants to the groups is performed based on these codes. The participants, the principal investigator, and the clinical caregivers (including the treating resident) are unaware of the type of the allocated intervention (melatonin or placebo). Outcome assessment and biomarker measurement are performed by laboratory personnel who are also unaware of the group allocation and the type of intervention. Data analysis is performed by the researcher using coded data (A and B), without access to the coding key. Unblinding of the codes is performed only after completion of the statistical analysis.