Solidarity trial

Solidarity trial
Title	Solidarity trial
Status	Completed
Sponsor	World Health Organization
Disease	COVID-19
Interventions	Remdesivir, Hydroxychloroquine, Lopinavir/ritonavir, Interferon beta-1a
Phase	Phase III
Start date	March 2020
End date	October 2020
Participants	~11,330
Locations	Over 30 countries

Solidarity trial. The Solidarity trial was a landmark international clinical trial launched by the World Health Organization in early 2020 to rapidly identify effective treatments for hospitalized patients with COVID-19. Designed as a large, simple, and adaptive study, it aimed to cut through the noise of numerous small studies and provide definitive answers on repurposed drugs. The trial represented an unprecedented global collaborative effort in medical research during the COVID-19 pandemic.

Background and rationale

The trial was conceived in the urgent context of the escalating COVID-19 pandemic, as global cases surged and healthcare systems faced immense pressure. The World Health Organization, under the leadership of Director-General Tedros Adhanom Ghebreyesus, sought to coordinate a global research response to prevent duplication and accelerate discovery. The rationale was to evaluate existing antiviral and anti-inflammatory drugs that showed promise in early laboratory or observational studies, thereby bypassing lengthy early-phase development. This approach was championed by scientists like John-Arne Røttingen and supported by health agencies worldwide, including the European Commission and the Government of Norway.

Design and methodology

The trial employed an innovative "master protocol" and adaptive, randomized, open-label design to allow for the flexible addition or removal of treatment arms based on emerging evidence. Its "large, simple trial" philosophy minimized data collection to essential outcomes like mortality and hospital discharge, enabling rapid enrollment even in overburdened settings. Statistical oversight was provided by an independent Data and Safety Monitoring Board to ensure integrity. The streamlined design contrasted with more complex trials like RECOVERY in the United Kingdom but shared the goal of generating robust results quickly, influencing other major studies such as those conducted by the National Institutes of Health.

Participating countries and institutions

Over 30 countries across six WHO regions eventually participated, enrolling patients from hundreds of hospitals. Key national coordinators included institutions like the Indian Council of Medical Research in India, the Ministry of Health (Iran) in the Islamic Republic of Iran, and research bodies in Canada, South Africa, and Brazil. The trial was centrally coordinated by the World Health Organization headquarters in Geneva, with crucial operational support from the University of Bern and the Research Council of Norway. This network created a unique global infrastructure for clinical research, fostering collaboration between nations often at different stages of the pandemic.

Treatments evaluated

The initial four treatment arms evaluated repurposed drugs selected for their potential mechanisms against SARS-CoV-2 or COVID-19 pathology. These included the antiviral Remdesivir (developed by Gilead Sciences), the antimalarial Hydroxychloroquine, the HIV protease inhibitor combination Lopinavir/ritonavir, and Interferon beta-1a, an immunomodulator. The Hydroxychloroquine arm was dropped early following external evidence, and the Lopinavir/ritonavir arm was later halted. The adaptive protocol allowed the trial to focus resources on the most promising candidates, a method also seen in concurrent trials like ACTT-1 led by the National Institute of Allergy and Infectious Diseases.

Results and findings

Interim results released in October 2020 indicated that none of the studied regimens—Remdesivir, Hydroxychloroquine, Lopinavir/ritonavir, or Interferon beta-1a—substantially reduced in-hospital mortality, initiation of ventilation, or duration of hospital stay. These findings, presented at a World Health Organization press briefing and later published in The New England Journal of Medicine, were pivotal. They provided strong evidence against the widespread use of these drugs for hospitalized COVID-19 patients, directly informing treatment guidelines from the World Health Organization and national bodies like the National Institutes of Health.

Impact and reception

The trial was widely hailed as a triumph of global scientific cooperation, demonstrating the feasibility of rapid, large-scale international research during a crisis. Its findings had immediate policy impacts, discouraging the use of ineffective therapies and saving resources. The model influenced subsequent trials for COVID-19 therapeutics and vaccines, including the COVAX facility. While some criticized its open-label design, its overall contribution to evidence-based medicine during the pandemic was endorsed by leaders from António Guterres of the United Nations to numerous public health experts. It stands as a key chapter in the history of the World Health Organization and global health responses.

Category:World Health Organization Category:COVID-19 pandemic Category:Clinical trials