Vancouver, Canada (26 August 2021) In June 2020, The TOGETHER Trial was established as an adaptive platform randomised clinical trial to test a range of potential treatments for COVID-19 that might be suitable for clinical use in a community setting in Brazil and other low- and middle-income countries. The trial specifically tested each treatment’s potential to prevent clinical worsening of COVID-19 requiring hospitalization.
The TOGETHER Trial is led by researchers in Canada, USA and Brazil. Investigators include those from McMaster University in Canada, Washington University in USA, and Cardresearch – Cardiologia Assistencial e de Pesquisa LTDA in Brazil. To date, the TOGETHER Trial has evaluated 7 different repurposed therapies.
One intervention the TOGETHER Trial is evaluating is fluvoxamine. Fluvoxamine is a safe and inexpensive drug typically used in forms of depression and related disorders. It is a well understood drug which has been in use since the 1990s and its safety profile is well understood. It was identified early in the pandemic for its potential to reduce the cytokine storm in COVID-19 patients.
A total of 1,472 patients had been randomly assigned to receive fluvoxamine or placebo. Patients were older than 50 years of age or had a known risk factor for developing severe COVID -19 disease. All patients are followed up for 28 days to determine if they experienced the primary outcome of retention in an emergency setting greater than 6 hours or COVID-19 associated hospitalization. Many other clinical outcomes are also evaluated.
The TOGETHER Trial evaluation of fluvoxamine was initiated on January 20th 2021 and stopped for effectiveness on August 6th 2021 at the recommendation of the Data and Safety Monitoring Committee. The committee recommended stopping as the treatment effects were convincing and no further patients needed to be recruited to the treatment arms. The drug resulted in approximately a 30% reduction in the primary outcome.
The TOGETHER Trial is one of only a few large Phase 3 platform randomized clinical trials to find evidence for an intervention that can be provided to patients before they become severely ill and prevent the likelihood of patients developing advanced disease. Findings from the TOGETHER Trial have the potential to change how COVID-19 is treated around the world as fluvoxamine is cheap, well understood, and widely available in most countries.
An earlier, smaller trial in the United States was published in JAMA and demonstrated a reduction in severe disease. The TOGETHER Trial partnered with the US investigators to evaluate its potential in Brazil, where COVID-19 has had a particularly negative effect on public health and resulted in hundreds of thousands of deaths.
More information on the trial readout will be shared in the coming weeks. The information has already been shared with major decision-making agencies including the National Institute of Health and the World Health Organization.
“The decision by the data safety and monitoring committee to stop the arm of fluvoxamine for signs of a positive effect is an exciting development for the trial, and for Brazil. We are in the midst of a surge again of COVID-19 and this is positive news that our trial findings may have important implications for outpatient care of COVID-19.” Professor Gilmar Reis - Brazil, Principal Investigator
“There are currently limited treatment options for the outpatient clinical management of COVID-19. A drug that costs only $4 per treatment of COVID-19 has major implications for care around the globe.” Professor Edward Mills – Canada, Principal Investigator
Notes to journalists:
Details on the trial and a pre-print of the preliminary findings are available at: www.togethertrial.com
Edward Mills is available for interviews. For more information, please contact:
Method of Research
Randomized controlled/clinical trial
Subject of Research