|Methods||Single site prospective, randomised trial.|
The trial continued for 12 weeks, though the follow-up period for enrollees was unclear.
|Participants||Area around Diglipur, Andaman Islands, India. Mix of residents including agricultural workers and adolescent school children. Two out of three participants were between the ages of 15 and 19 years. Gender distribution was not disclosed. Exclusion criteria included pregnancy, lactation, chronic disease, or an ongoing medication regimen of any kind.|
|Interventions||Pre-exposure prophylaxis with weekly administration of two doses of 100 mg doxycycline spaced twelve hours apart or vitamin B complex tablets (intended placebo).|
1025 participants were randomised into two groups, though analyses were reported on only 782.
Group I: 386 participants (513 enrolled) - doxycycline.
Group II: 396 participants (512 enrolled) - vitamin B complex tablets as placebo.
|Outcomes||The primary outcome was laboratory identified infection.|
|Notes||Withdrawal criteria were broad and included any illness, a missed dose, or the prescription of additional antibiotics. Manner of exclusion of leptospirosis in such instances and the method of subsequent handling of that participant's data was not disclosed.The morning dose was directly observed, and evening dose adherence was logged by a visiting field worker. Approximately twenty-eight per cent of participants in each group had a baseline Leptospira titer greater than 1:100.|
Gastric irritation was the most common adverse effect reported. In Group I three participants were withdrawn for adverse events. One of these persons developed an erythematous rash after the first dose, while the other two persons withdrawn experienced gastritis with persistent stomach pain and vomiting. Rates of less severe adverse events were not fully characterized.
|Risk of bias|
|Bias||Authors' judgement||Support for judgement|
|Adequate sequence generation?||Unclear risk||Unclear.|
|Allocation concealment?||Unclear risk||Sealed envelopes, but no information if they were opaque.|
|Unclear risk||Patient and laboratory were explicitly identified as blinded, but whether clinical evaluators were blind to participants' assignment was not clear. Also, the degree to which the vitamin B complex tablets used for placebo resembled the intervention medication was not disclosed.|
|Incomplete outcome data addressed? |
|High risk||243 enrollees were not included in analyses nor were their data reported. While laboratory findings were relayed in detail, clinical findings were not.|
|Free of selective reporting?||Low risk||Death and adverse events were included in their reporting of the data.|
|Free of baseline imbalance?||Unclear risk||Age was well disclosed, though gender distribution was less clear. Also, the nature of potential exposures was not delineated by group - for instance, distribution of agricultural workers and students between the two groups.|
|Free of early stopping?||Unclear risk||Unclear.|
|Free of academic bias?||Low risk||Yes.|
|Free of source of funding bias?||Unclear risk||Pfizer provided doxycycline.|