Exclusion criteria

Pregnant or breast-feeding women, patients who are simultaneously participating in another clinical trial with an unlicensed drug or who have done so within a one-month period, patients not willing to participate in the study, patients with a known hypersensitivity to any of the drugs, and moribund patients.

This study was conducted in the department of surgery of a tertiary care hospital in Mumbai, India. The subjects were in-patients from six wards of the department. Patients were enrolled and assessed between August 2013 and October 2015.

A set of 463 patients were screened on a continuous basis (Fig. 1), out of which 150 patients met all criteria. Thus 75 blocks were enrolled. Within each block, the patients were randomly assigned to the treatment groups by computer-generated random assignment. A set of 15 patients were non-compliant with the wound-dressing protocol or wished to be discharged for home care. In such cases, the entire block (total=15 blocks, n=30) was discarded from the study analysis, maintaining an allocation ratio of 1:1. Thus 60 blocks (n=120) completed the trial.

Group A (TCDO) was treated with a solution of 100 mL that contained 1.037 mg tetrachlorodecaoxide in an aqueous base. Group B (SOS) was treated with commonly used solution prepared as per patented Microcyn technology (Oculus Innovative Sciences, Petaluma, CA, USA). The agents were applied using disposable dark-tinged spray pump bottles. Wound dressing was done daily, twice a day, by first-year residents (PGY1) with test/comparator agents, as per institutional protocol. After a 48-hour post-admission wash out period of standard care (scrubbing+povidone dressing), the patients were assessed on day 0 (baseline), 1, 4, 7, 14, 21 28, 42, and 56. On each assessment day, the following procedure was followed: (1) Step 1: Initial examination of the wound was done. The investigators assessed the wounds as per the protocol, including measurement of wound area, scoring of wound exudation and tissue type, and usage of the PUSH Tool. (2) Step 2: The wound was cleaned thoroughly and any necrotic tissue was debrided/removed with forceps. (3) Step 3: Dressing was done with gauze after applying the test/comparator agent to the wound surface, so as to form a thin moist film of agent on the entire surface of the wound.

Wound recovery was assessed by decrease in wound size (approximate area), which was the primary efficacy variable, as well as improvement in scores of wound exudation and wound tissue type as per the PUSH Tool. Total recovery was measured by the total scores obtained using the PUSH Tool. The scores of both treatment groups were compared with each other for analysis of the comparative efficacies of the treatment agents. For wound area, the longest distances in length (centimetres) and width (centimetres) were measured and multiplied to give an approximate area of wound (square centimetres). In addition, this area was scored as per the PUSH Tool (ranging from 0 to 10). Wound exudation was scored according to its observed quantity (none, light, moderate, and heavy awarded 0, 1, 2, and 3 points respectively, as included in the PUSH Tool), quality (serous, sero-sanguinous, and purulent awarded 1, 2, and 3 points respectively), and odor (if present, awarded 1 point). Thus the range of total score for wound exudation is 0–7 points. Wound tissue type was scored as per the PUSH Tool (epithelial tissue, granulation tissue, slough, and necrotic tissue awarded 1, 2, 3, and 4 points respectively). Additionally, total scores as given by the PUSH Tool on basis of wound area, observed quantity of wound exudation, and wound tissue type were computed. For subjective assessment of pain felt by the patient, the visual analogue scale (range, 0–10; 0 indicates least and 10 the maximum amount of pain) was used before the wound dressing was done. As per hospital standard of care protocols, all patients with infected ulcers were administered the antibiotic metronidazole. Wound culture sensitivity, complete blood check-up, renal and liver function tests, serum protein values, and blood sugar values were recorded for days 0, 14, 28, and 56 only. After day 56, the treatment was continued as per requirement; however, no assessments were included in the trial records.

Information on adverse events/side effects was to be obtained at each assessment visit (except the visit on day 0) as response to a non-leading question: "Have you had any new symptoms or increase in discomfort since your last assessment visit?" Additionally, any abnormal findings from physical examination or laboratory tests considered as adverse events/side effects by the investigator had to be documented as such.