ANTICOV is testing several treatment combinations, and pre-planned interim analyses are regularly conducted to assess if any of the tested arms could be stopped before the trial ends, if they show signals of very high – or lack of – efficacy. Following its third interim efficacy analysis performed on a total of 946 patients enrolled in all arms with a known last visit (day 21) outcome, the ANTICOV independent Data and Safety Monitoring Board (DSMB) concluded that early futility (meaning very low efficacy) has been demonstrated for the nitazoxanide/inhaled ciclesonide arm of the trial.
Interim efficacy analyses showed that 1.13% of patients (5 of 443) in the control arm (paracetamol) saw their symptoms deteriorate (their blood oxygen level decreased below the 93% threshold) compared to 3.25% of patients (15 of 462) treated with the nitazoxanide/ciclesonide combination. The DSMB therefore concluded that there has been no convincing evidence of the efficacy of this combination on COVID-19 patients with mild to moderate symptoms, compared to the control arm. These results show that nitazoxanide/ciclesonide combination treatment has very little chance of preventing progression to severe symptoms of COVID-19 compared to the control arm.
The DSMB also concluded that no safety issues were detected.
The ANTICOV Joint Steering Committee endorsed the recommendation from the DSMB to stop recruitment in this arm.
"We need large, context-specific treatment trials for low- and middle-income countries that have largely been left out of COVID-19 research, to guide us on what works and what does not," said Nathalie Strub-Wourgaft, head of the COVID-19 response at the Drugs for Neglected Diseases initiative (DNDi), which is coordinating the trial. "This result achieved by the hard work of investigators in ANTICOV partner countries illustrates the value of platform trials. This is important evidence that was generated in Africa, by African researchers with their international partners, and that will inform decisions both in Africa and globally."
The ANTICOV trial is an open-label, randomized, comparative, adaptive platform trial that aims to identify COVID-19 treatments that are optimized for use in resource-limited settings and that can prevent progression to severe disease and potentially limit transmission. ANTICOV’s flexible and innovative trial design allows for treatments to be added or removed as evidence emerges.
ANTICOV will continue to recruit patients into its other treatments arms, including the recently announced combination drugs fluoxetine and budesonide.
Major funding for the ANTICOV consortium is provided by the German Federal Ministry of Education and Research (BMBF) through KfW and by the global health agency Unitaid as part of ACT-A. Additional support comes from the European & Developing Countries Clinical Trials Partnership (EDCTP) – under its second programme supported by the European Union with additional funding from the Swedish government – the Starr International Foundation and the Stavros Niarchos Foundation (SNF).