Several master protocols that can test multiple drugs in parallel are now underway in COVID-19. By streamlining patient recruitment, standards of care, data collection and more, these could generate more robust data than stand-alone trials, and enable more efficient evaluation of the proposed drug pipeline.

For now, these trials are still testing repurposed agents, primarily in hospitalized patients with confirmed COVID-19.

The UK’s 9,600-patient RECOVERY trial, for instance, is randomizing patients into five arms: the HIV drugs lopinavir–ritonavir; the steroid dexamethasone; the antimalarial hydroxychloroquine; the antibiotic azithromycin; and the anti-inflammatory IL-6 blocker tocilizumab.

The WHO’s SOLIDARITY trial is set up such that countries around the world can participate, regardless of their infrastructural capabilities. It had recruited 1,200 patients by 21 April. Treatment arms consist of Gilead’s RNA-polymerase inhibitor remdesivir, chloroquine or hydroxychloroquine, lopinavir–ritonavir, and lopinavir–ritonavir plus the immune-modulatory agent IFNβ1a.

The NIAID’s ACTT trial enrolled over 1,000 hospitalized patients with COVID-19 onto remdesivir or placebo. Preliminary results from this trial prompted the FDA to issue an Emergency Use Authorization for remdesivir. A follow-on 1,000-patient trial called ACTT 2 is now testing Lilly’s anti-inflammatory JAK inhibitor baricitinib in combination with remdesivir, versus placebo plus remdesivir.

But agents also need to be tested earlier in the course of disease. The UK’s 3,000-patient PRINCIPLE trial is enrolling high-risk and older patients with symptoms of disease to reduce the need for hospitalization. A first arm is testing hydroxychloroquine, and a second will test azithromycin.

REMAP-CAP, first set up for community-acquired pneumonia, has added a COVID-19 component. To date, 420 patients have been recruited. In addition to hydroxychloroquine, lopinavir–ritonavir, IFNβ, corticosteroid strategies and macrolide therapy, it is also being amended to evaluate the IL-1 receptor antagonist anakinra and the IL-6 blockers tocilizumab and sarilumab.

With the COVID-19 pipeline growing, there is also a need for trials that can generate preliminary data to prioritize follow-on work. The UK’s 1,800-patient ACCORD trial in hospitalized patients with COVID-19 is taking this on, setting out to test six agents that could then be advanced into larger umbrella trials. As Nature Reviews Drug Discovery went to press, disclosed agents in this trial included BerGenBio’s AXL inhibitor bemcentinib, AstraZeneca’s IL-33 mAb MEDI-3506 and AstraZeneca’s BTK inhibitor acalabrutinib.

The NIH has also setup ACTIV, to prioritize vaccine and drug candidates for clinical trials.

Over 115 vaccine candidates have also been proposed. The WHO is working on a master protocol for the most promising vaccines.