After the approval of the study protocols by the Mashhad University of Medical Sciences Institutional Review Board, we conducted a single-center, double-blind, randomized clinical trial to determine the effectiveness of postoperative oral administration of cephalexin plus metronidazole compared with placebo for 48 h after CS for the prevention of SSI among obese women. Participants were recruited from April 2019 to February 2020 at the Ommolbanin Hospital, affiliated with Mashhad University of Medical Sciences. Written informed consent was obtained from all patients postoperatively.
Women were eligible for randomization if they aged at least 15 years, lived in Mashhad, had a pregnancy BMI of 30 or higher, had a final plan for cesarean delivery at Ommolbanin Hospital, and were able to come to the Ommolbanin Hospital for follow-up. Besides, both elective and emergency CS were recruited in the study. Patients were excluded if they had to take antibiotics in the postpartum period for any reason or had a preterm delivery, multiple births, amniorrhexis, immunodeficiency syndromes, known or suspected allergies to cephalexin or metronidazole, or diabetes mellitus needing insulin therapy.
All subjects gave written informed consent to participate in the study and then were randomized to the intervention group, receiving both 500 mg oral cephalexin and 500 mg oral metronidazole every 8 h for 6 doses; and the placebo group.
The CS was performed in standard practice by residents, fellows, and attending physicians. Prior to the skin incision, the abdomen was cleansed using the povidone-iodine solution, standard sterile draping was performed and prophylactic Cefazolin (2 g) was injected intravenously. Pfannenstiel skin incision was performed for all cases and uterine was incised using Kerr incision. Surgical dressings were removed 24 h postoperatively and the incision was irrigated using a normal saline solution. The surgical site was cleansed using povidone-iodine solution 48 h postoperatively.
Participants were randomly assigned to intervention and control groups using the simple randomization procedure. Inside 210 opaque, sealed and stapled envelopes was the word T (treatment group) and inside another 210 opaque, sealed and stapled envelopes was the word P (placebo group). All subjects were asked to pick an envelope and the card inside told if the patient was to be in the treatment or placebo group. Only the statistical analyzer was known about what each envelope included.
Cephalexin and metronidazole and their indistinguishable placebos were put in packs named T (treatment group) and P (placebo group) according to a computer-generated randomization list. In terms of appearance and shape, the placebo was exactly the same as the original antibiotics, in the way that placebo metronidazole was exactly the same as metronidazole in the form of a white round tablet and placebo cephalexin was exactly the same as the original antibiotic, as a yellow capsule.
First doses of oral Cephalexin, 500 mg, and oral Metronidazole, 500 mg, were administered 8 h after preoperative intravenous injection of prophylactic Cefazolin (2 g) and were continued every 8 h for another 5 doses.
Cephalexin, Metronidazole, Cephalexin placebo and Metronidazole placebo were all indistinguishable and produced by the Sobhan Pharmaceutical Company®.
Follow-up examinations at one week and two weeks postpartum were performed by the gynecologist of the study. All subjects were examined for drug adverse effects and symptoms of SSI such as fever (temperature equal to or greater than 37.5 Celsius), cellulitis, uterine tenderness, and wound separation.
Independent t-test or Mann– Whitney test was used to examine the differences of normally-distributed quantitative variables between the two groups. The Chi-square test or Fisher's exact test was used to compare differences in qualitative variables between the two groups. p-values of less than 0.05 were considered to be statically significant. All statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) version 23 (SPSS Inc., Chicago, IL, USA).
We estimated the sample size for our study assuming a baseline rate of SSI of 6.4% in the treatment group and 15.4% in the placebo group on the basis of a study conducted by Amy M. Valent et al. in 2017 [13]. We predicted a 50% lower risk of SSI in the treatment group than in the placebo group. To have 80% power to detect a 50% difference in the rates of SSI, we estimated that the study needed 188 participants in each group (α = 0.05). In order to accommodate a 10% rate of postoperative loss to follow-up, we anticipated enrolling 210 participants in each group.
The ethical approval for conducting this study was obtained from the ‘Ethical Committee of the Mashhad University of Medical Sciences (Registration code: IR.MUMS.MEDICAL.REC.1397.733). Also, the study protocol was approved by the Iranian Registry of Clinical Trials (IRCTID: IRCT20200608047685N2) on 2021-03-15.