Ivermectin Does Not Reach Primary Endpoint in Burkina Faso Malaria Trial
Sunil Parikh, MD, MPH, discusses the trial’s findings, noting no significant difference in malaria incidence (1.78 vs 1.84 cases per 100 person-weeks).
A large clinical trial in Burkina Faso, called RIMDAMAL II (NCT03967054), found that repeated high-dose ivermectin mass drug administration (MDA) did not significantly reduce malaria incidence in children when integrated with seasonal malaria chemoprevention (SMC). The study, published in The Lancet, evaluated ivermectin’s safety and efficacy in killing malaria-carrying mosquitoes that feed on treated individuals. Despite its safety and potential to impact mosquito survival, ivermectin MDA did not provide meaningful malaria control benefits in this setting, leading researchers to suggest further studies to assess its role in vector control under varied epidemiological conditions.
While mosquito survival decreased in the ivermectin group immediately post-treatment in 2019 (P<.0001), this effect was not sustained. Additionally, children in the ivermectin group showed greater improvements in hemoglobin levels (P = .007). Although, external factors such as the government’s distribution of insecticide-treated nets during the trial and the high diversity of parasites and mosquito species may have influenced the results.
The phase 3 double-blind, placebo-controlled, cluster-randomized trial was conducted across 14 villages over two rainy seasons (2019–2020). Communities were assigned to receive either ivermectin or a placebo, with over 4,000 participants monitored. Malaria incidence among children remained similar between the intervention (1.78 cases per 100 person-weeks) and control groups (1.84 cases per 100 person-weeks; P = .8723).
Part 2 of our interview with Sunil Parikh, MD, MPH, lead investigator and professor at the Yale School of Public Health, addressed some key aspects of the study, particularly around the safety and efficacy of ivermectin. He explained, “We began this study before the COVID pandemic, and the work had been ongoing for over a decade, with some preliminary research. However, at the time we conducted the study, the dose of ivermectin we administered—repeatedly for 3 consecutive days, and then every month—hadn't been thoroughly tested for safety. While we had every reason to believe it would be safe, part of our trial's goal was to confirm whether or not this repeated high-dose ivermectin regimen was safe.”
Parikh also noted that, during the COVID pandemic, some groups began using ivermectin as a potential treatment for the virus, despite its ineffectiveness. “Some of these groups were administering high doses, similar to what we were using. But, when we reviewed all the data from our study, we found that repeated doses of ivermectin were, in fact, safe. In fact, by the end of the trial, the villages receiving repeated doses of ivermectin reported fewer adverse events. It’s a bit difficult to explain, but one hypothesis is that we may have eliminated other contributing factors.”
Although he emphasized, “That said, it’s important to note that our primary outcome was not achieved.”
The trial’s results raise important questions about the role of ivermectin in malaria control. Parikh highlighted the ongoing challenges in malaria research, “There have been about 3 or 4 trials, including ours, that have been completed or are forthcoming in the past and next year. On the whole, these studies have not supported the efficacy of ivermectin in reducing incidence, except for one trial that showed a reduction in prevalence. So, the weight of the current evidence suggests that ivermectin, as it was used in these trials, hasn’t been effective,” he said.
“These trials did face a lot of challenges, and some of those challenges are just part of the reality of conducting trials. But I think we’re at a critical crossroads in malaria control for several reasons," he said. "Progress has been difficult in recent years, and we're now facing significant challenges in terms of global funding.”
Parikh concluded by emphasizing the continued importance of innovation in malaria control. “I just want to emphasize that malaria remains a major issue, and we need continued investment to make further progress. Now is not the time to halt innovative trials and novel interventions—they’re more crucial than ever.”
In the first part of our interview with Parikh we discussed the broader challenges of malaria control and the rationale behind integrating ivermectin with seasonal malaria chemoprevention: Insights from Phase 3 Trial in Burkina Faso on Ivermectin’s Role in Malaria Control
