Oral doxycycline for the prevention of postoperative trachomatous trichiasis in Ethiopia: a randomised, double-blind, placebo-controlled trial

Abstract

Summary: Background: Trachomatous trichiasis is treated surgically to prevent sight loss. Unfavourable surgical outcomes remain a major challenge. We investigated the hypothesis that doxycycline might reduce the risk of postoperative trichiasis following surgery in patients with trachomatous trichiasis through anti-matrix metalloproteinase and anti-inflammatory activity. Methods: In this randomised, double-blind, placebo-controlled trial, adults (aged >18 years) with upper lid trachomatous trichiasis in association with tarsal conjunctive scarring were recruited through community-based screening and surgical outreach campaigns in Ethiopia. Individuals who had previously had eyelid surgery were excluded. Participants were randomly assigned (1:1), with random block sizes of four or six, to receive oral doxycycline (100 mg once a day) or placebo for 28 days immediately after trichiasis surgery. Randomisation was stratified by surgeon. Patients, investigators, surgeons, and all other study team members were masked to study group allocation and treatment. Participants were examined at 10 days, and 1, 6, and 12 months after surgery. The primary outcome was the cumulative proportion of individuals who developed postoperative trichiasis by 12 months. Primary analyses were done in all participants who attended at least one of the four follow-up assessments. Safety analyses were done in all participants who attended either the 10 day or 1 month follow-up assessments. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201512001370307. Findings: Between Dec 21, 2015, and April 6, 2016, 1000 patients with trichiasis were enrolled and randomly assigned to treatment (499 patients to doxycycline, 501 patients to placebo). All but one participant attended at least one follow-up assessment. Thus, 999 participants were assessed for the primary outcome: 498 in the doxycycline group and 501 in the placebo group. By month 12, 58 (12%) of 498 patients in the doxycycline group and 62 (12%) of 501 patients in the placebo group had developed postoperative trichiasis (adjusted odds ratio 0·91, 95% CI 0·61 to 1·34, p=0·63), with a risk difference of −0·5% (–4·5% to 3·5%). Significantly more patients in the doxycycline group had an adverse event than in the placebo group (18 [4%] of 498 vs six [1%] of 501; odds ratio 3·09, 95% CI 1·21–7·84; p=0·02). The most frequent adverse events in the doxycycline group were gastritis symptoms (n=9), constipation (n=4), and diarrhoea (n=4). Interpretation: Doxycycline did not reduce the risk of postoperative trichiasis and is therefore not indicated for the improvement of outcomes following trachomatous trichiasis surgery. Surgical programmes should continue to make efforts to strengthen surgical training and supervision to improve outcomes. Funding: The Wellcome Trust.