COVID-19: multi-arm, multi stage adaptive clinical trial (CoV-MAMS)

The coronavirus epidemic is a global health emergency. The infection can, in a minority of cases, cause serious lung disease requiring hospital-care and even death. Whilst general hospital care can improve patients’ recovery, there are currently no specific medicines for this infection. The best way to prove that medicines are effective and safe is through clinical trials which compare the new medicine against normal care.

Clinical trials of two of the most promising medicines have already enrolled patients in China. There are, however, many other medicines that have been proposed for the treatment of patients with the novel coronavirus.

We will start a new trial in the UK to test up to four additional medicines. Patients hospitalised with confirmed coronavirus infection will be invited to join the trial and we will assess whether the new medicines are safe and can improve patients’ recovery.

We will use a flexible design that allows us to add new medicines as they become available. The trial will start by testing two medicine, a drug that may slow down the replication of the virus and a drug that may reduce the inflammation associated with the infection. Other medicines will be added when they become available.

This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project.

Medicines to prevent and effectively treat 2019 coronavirus disease (COVID-19), especially severe lower respiratory tract (LRT) illness, would save lives and reduce healthcare pressures. Randomised controlled trials (RCTs) are ongoing in China of lopinavir/ritonavir [ChiCTR2000029308] and remdesivir [NCT04257656 and NCT04252664]. Additional potential therapeutics are being considered by the WHO. Building on our existing experience and capabilities, we are proposing to implement a multi-arm, multi-stage (MAMS) RCT. This trial will be designed to evaluate up to four experimental therapeutics in a flexible, adaptive framework. MAMS designs have been shown to be more efficient than sequential RCTs or factorial designs.
The trial will enrol patients hospitalised with laboratory confirmed COVID-19. Patients will initially be randomised equally to receive one of up to 4 active treatments or control. Should not all active arms be available at study onset, patients will be randomized between available active arms and control. The trial will commence with two active arms, lopinavir/ritonavir and low dose dexamethasone. Additional active arms will be added as data and drug availability allow.