Unexpected adverse reactions during a clinical trial in rural west Africa.

Ribavirin has been used widely in various clinical trials, without significant adverse effects beyond reversible, mild anemia. Since 1978 intravenous ribavirin has been used to treat Lassa fever in a remote area of Eastern Sierra Leone, West Africa. In March 1991, brief episodes of rigors in patients receiving ribavirin were reported. An immediate investigation found that 27/93 patients (29%) had records in 1990/91 of at least one episode, the strongest association being with survival of Lassa fever (P = 0.0001). The occurrence or number of rigors in an individual patient was unassociated with sex, age, weight, volume of loading dose, cumulative dose, administration of other drugs, use of intravenous lines or heparin traps. In a review of 12 years of ribavirin administration, 74/2117 injections sampled (3.5%) were associated with a record of rigors. Most occurred before 08.00 h (P less than 0.0001), between 0 and 30 min after injection, lasted 2-45 min, and clustered towards the end of the treatment course (P less than 0.0001). There was no association with drug lot or individual vials. Drug was being given as a bolus (less than 1 min). Since slowing the infusion rate, no further episodes have been reported. Epidemiologic techniques are important tools in rapid assessment of unexpected events particularly when conducting trials in remote locations.