High-dose immunosuppression to prevent death after paraquat self-poisoning - a randomised controlled trial

Context Intentional self-poisoning with the herbicide paraquat has a very high case-fatality and is a major problem in rural Asia and Pacific.
Objectives We aimed to determine whether the addition of immunosuppression to supportive care offers benefit in resource poor Asian district hospitals.
Materials and Methods We performed a randomised placebo-controlled trial comparing immunosuppression (intravenous cyclophosphamide up to 1g/day for two days and methylprednisolone 1g/day for 3 days, and then oral dexamethasone 8mg three-times-a-day for 14 days) with saline and placebo tablets, in addition to standard care, in patients with acute paraquat self-poisoning admitted to six Sri Lankan hospitals between 1st March 2007 and 15th November 2010. The primary outcome was in hospital mortality.
Results 299 patients were randomised to receive immunosuppression (147) or saline/placebo (152). There was no significant difference in in-hospital mortality rates between the groups (immunosuppression 78 [53%] vs. placebo 94 [62%] (Chi squared test 2.4, p=0.12). There was no difference in mortality at 3 months between and immunosuppression (101/147 [69%]) and placebo groups (108/152 [71%]); (Mortality reduction 2%, 95% CI: -8 to +12%). A Cox model did not support benefit from high-dose immunosuppression but suggested potential benefit from the subsequent two weeks of dexamethasone.
Conclusions We found no evidence that high dose immunosuppression improves survival in paraquat-poisoned patients. The continuing high mortality means further research on the use of dexamethasone and other potential treatments is urgently needed.