Solidarity trial

Last updated

The Solidarity trial for treatments is a multinational Phase III-IV clinical trial organized by the World Health Organization (WHO) and partners to compare four untested treatments for hospitalized people with severe COVID-19 illness. [1] [2] The trial was announced 18 March 2020, [1] and as of 6 August 2021, 12,000 patients in 30 countries had been recruited to participate in the trial. [3]


In May, the WHO announced an international coalition for simultaneously developing several candidate vaccines to prevent COVID-19 disease, calling this effort the Solidarity trial for vaccines. [4]

The treatments being investigated are remdesivir, lopinavir/ritonavir combined, lopinavir/ritonavir combined with interferon-beta, and hydroxychloroquine or chloroquine. Hydroxychloroquine or chloroquine investigation was discontinued in June 2020 due to concluding that it provided no benefit.

Solidarity trial for treatment candidates

The trial intends to rapidly assess thousands of COVID-19 infected people for the potential efficacy of existing antiviral and anti-inflammatory agents not yet evaluated specifically for COVID-19 illness, a process called "repurposing" or "repositioning" an already-approved drug for a different disease. [2] [5]

The Solidarity project is designed to give rapid insights to key clinical questions: [2] [5]

Enrolling people with COVID-19 infection is simplified by using data entries, including informed consent, on a WHO website. [2] After the trial staff determine the drugs available at the hospital, the WHO website randomizes the hospitalized subject to one of the trial drugs or to the hospital standard of care for treating COVID-19. The trial physician records and submits follow-up information about the subject status and treatment, completing data input via the WHO Solidarity website. [2] The design of the Solidarity trial is not double-blind – which is normally the standard in a high-quality clinical trial – but WHO needed speed with quality for the trial across many hospitals and countries. [2] A global safety monitoring board of WHO physicians examine interim results to assist decisions on safety and effectiveness of the trial drugs, and alter the trial design or recommend an effective therapy. [2] [5] A similar web-based study to Solidarity, called "Discovery", was initiated in March across seven countries by INSERM (Paris, France). [2] [6]

The Solidarity trial seeks to implement coordination across hundreds of hospital sites in different countries – including those with poorly-developed infrastructure for clinical trials – yet needs to be conducted rapidly. According to John-Arne Røttingen, chief executive of the Research Council of Norway and chairman of the Solidarity trial international steering committee, the trial would be considered effective if therapies are determined to "reduce the proportion of patients that need ventilators by, say, 20%, that could have a huge impact on our national health-care systems." [7]

Adaptive design

According to the WHO Director General, the aim of the trial is to "dramatically cut down the time needed to generate robust evidence about what drugs work", [8] a process using an "adaptive design". [9] [10] The Solidarity and European Discovery trials apply adaptive design to rapidly alter trial parameters when results from the four experimental therapeutic strategies emerge. [6] [11]

Adaptive designs within ongoing Phase III-IV clinical trials – such as the Solidarity and Discovery projects – may shorten the trial duration and use fewer subjects, possibly expediting decisions for early termination to save costs if interim results are negative. [6] [9] [10] If the Solidarity project shows early evidence of success, design changes across the project's international locations can be made rapidly to enhance overall outcomes of affected people and hasten use of the therapeutic drug. [1] [6]

Treatment candidates under study

The individual or combined drugs being studied in the Solidarity and Discovery projects are already approved for other diseases. [2] They are: [2] [6]

Due to safety concerns and evidence of heart arrhythmias leading to higher death rates, the WHO suspended the hydroxychloroquine arm of the Solidarity trial in late May 2020, [13] [14] then reinstated it, [15] then withdrew it again when an interim analysis in June showed that hydroxychloroquine provided no benefit to hospitalized people severely infected with COVID-19. [12]

In October 2020, the World Health Organization Solidarity trial produced an interim report concluding that its "remdesivir, hydroxychloroquine, lopinavir and interferon regimens appeared to have little or no effect on hospitalized COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay." [16] Gilead – the manufacturer of remdesivir – criticized the Solidarity trial methodology after it showed no benefit of the treatments, claiming that the international nature of the Solidarity trial was a weakness, whereas many experts regard the multinational study as a strength. [17] Purchase agreements between the EU and Gilead for remdesivir and granting of its Emergency Use Authorization by the US FDA during October were questioned by Solidarity trial scientists as not based on positive clinical trial data, when the interim analysis of the Solidarity trial had found remdesivir to be ineffective. [17]

In January 2022, the Canadian component of the Solidarity trial reported that in-hospital people with COVID-19 treated with remdesivir had lower death rates (by about 4%) and reduced need for oxygen (less by 5%) and mechanical ventilation (less by 7%) compared to people receiving standard-of-care treatments. [18]

Support and participation

During March, funding for the Solidarity trial reached US$108 million from 203,000 individual donations, charitable organizations and governments, with 45 countries involved in financing or trial management. [1] [19] As of 1 July 2020, nearly 5,500 patients in 21 countries of 39 that have approval to recruit were recruited to participate in the trial. More than 100 countries in all 6 WHO regions have expressed interest in participating. [3]

Solidarity trial for vaccine candidates

The WHO has developed a multinational coalition of vaccine scientists defining a Global Target Product Profile (TPP) for COVID-19, identifying favorable attributes of safe and effective vaccines under two broad categories: "vaccines for the long-term protection of people at higher risk of COVID-19, such as healthcare workers", and other vaccines to provide rapid-response immunity for new outbreaks. [4] The international TPP team was formed to 1) assess the development of the most promising candidate vaccines; 2) map candidate vaccines and their clinical trial worldwide, publishing a frequently-updated "landscape" of vaccines in development; [20] 3) rapidly evaluate and screen for the most promising candidate vaccines simultaneously before they are tested in humans; and 4) design and coordinate a multiple-site, international randomized controlled trial   the Solidarity trial for vaccines [21]   to enable simultaneous evaluation of the benefits and risks of different vaccine candidates under clinical trials in countries where there are high rates of COVID-19 disease, ensuring fast interpretation and sharing of results around the world. [4] The WHO vaccine coalition will prioritize which vaccines should go into Phase II and III clinical trials, and determine harmonized Phase III protocols for all vaccines achieving the pivotal trial stage. [4]

Solidarity Plus Trial

The WHO announced in August 2021 that it will roll out the next phase Solidarity trial under the name Solidarity PLUS trial in 52 countries. The trial will enroll hospitalized patients to test three new drugs for potential treatment of COVID-19. These drugs include artesunate, imatinib and infliximab. The selection of these therapies was done by an independent expert panel of WHO. These drugs are already used for other indications: artesunate is used for malaria, imatinib for cancers, and infliximab, an anti-TNF agent is used for Crohn’s Disease and rheumatoid arthritis. The drugs will be donated for the purpose of trial by their manufacturers.

See also

Related Research Articles

Ritonavir Antiretroviral medication

Ritonavir, a protease inhibitor sold under the brand name Norvir, is an antiretroviral medication used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Often a low dose is used with other protease inhibitors. It may also be used in combination with other medications for hepatitis C. It is taken by mouth. The tablets of ritonavir are not bioequivalent to capsules as tablets may result in higher peak plasma concentrations.

Chloroquine Medication used to treat malaria

Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medication. Chloroquine is also occasionally used for amebiasis that is occurring outside the intestines, rheumatoid arthritis, and lupus erythematosus. While it has not been formally studied in pregnancy, it appears safe. It was studied to treat COVID-19 early in the pandemic, but these studies were largely halted in the summer of 2020, and is not recommended for this purpose. It is taken by mouth.

Hydroxychloroquine Antimalarial medication

Hydroxychloroquine, sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine. Other uses include treatment of rheumatoid arthritis, lupus, and porphyria cutanea tarda. It is taken by mouth, often in the form of hydroxychloroquine sulfate.

Association of American Physicians and Surgeons Conservative political advocacy organization

The Association of American Physicians and Surgeons (AAPS) is a politically conservative non-profit association that promotes medical misinformation, such as HIV/AIDS denialism, the abortion-breast cancer hypothesis, vaccine and autism connections, and homosexuality reducing life expectancy. The association was founded in 1943 to oppose a government attempt to nationalize health care. The group has included notable members, including American Republican politicians Ron Paul, Rand Paul and Tom Price.


Lopinavir is an antiretroviral of the protease inhibitor class. It is used against HIV infections as a fixed-dose combination with another protease inhibitor, ritonavir (lopinavir/ritonavir).

An Emergency Use Authorization (EUA) in the United States is an authorization granted to the Food and Drug Administration (FDA) under sections of the Federal Food, Drug, and Cosmetic Act as added to and amended by various Acts of Congress, including by the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA), as codified by 21 U.S.C. § 360bbb-3, to allow the use of a drug prior to approval. It does not constitute approval of the drug in the full statutory meaning of the term, but instead authorizes the FDA to facilitate availability of an unapproved product, or an unapproved use of an approved product, during a declared state of emergency from one of several agencies or of a "material threat" by the Secretary of Homeland Security.

Lopinavir/ritonavir Combination medication for HIV/AIDS

Lopinavir/ritonavir (LPV/r), sold under the brand name Kaletra among others, is a fixed-dose combination antiretroviral medication for the treatment and prevention of HIV/AIDS. It combines lopinavir with a low dose of ritonavir. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlestick injury or other potential exposure. It is taken by mouth as a tablet, capsule, or solution.


Baricitinib, sold under the brand name Olumiant among others, is a drug for the treatment of rheumatoid arthritis (RA) in adults whose disease was not well controlled by tumor necrosis factor (TNF) inhibitors. It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2. The drug is approved for medical use in the European Union and in the United States. An important side effect of JAK inhibitors is serious bacterial, mycobacterial, fungal and viral infections.

Remdesivir Antiviral drug

Remdesivir, sold under the brand name Veklury, is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences. It is administered via injection into a vein. During the COVID-19 pandemic, remdesivir was approved or authorized for emergency use to treat COVID‑19 in around 50 countries.


Danoprevir (INN) is an orally available 15-membered macrocyclic peptidomimetic inhibitor of NS3/4A HCV protease. It contains acylsulfonamide, fluoroisoindole and tert-butyl carbamate moieties. Danoprevir is a clinical candidate based on its favorable potency profile against multiple HCV genotypes 1–6 and key mutants (GT1b, IC50 = 0.2–0.4 nM; replicon GT1b, EC50 = 1.6 nM). Danoprevir has been evaluated in an open-label, single arm clinical trial in combination with ritonavir for treating COVID-19 and favourably compared to lopinavir/ritonavir in a second trial.

COVID-19 drug repurposing research Drug repurposing research related to COVID-19

Drug repositioning is the repurposing of an approved drug for the treatment of a different disease or medical condition than that for which it was originally developed. This is one line of scientific research which is being pursued to develop safe and effective COVID‑19 treatments. Other research directions include the development of a COVID‑19 vaccine and convalescent plasma transfusion.

COVID-19 drug development Preventative and therapeutic medications for COVID-19 infection

COVID-19 drug development is the research process to develop preventative therapeutic prescription drugs that would alleviate the severity of coronavirus disease 2019 (COVID-19). From early 2020 through 2021, several hundred drug companies, biotechnology firms, university research groups, and health organizations were developing therapeutic candidates for COVID-19 disease in various stages of preclinical or clinical research, with 419 potential COVID-19 drugs in clinical trials, as of April 2021.

There is no specific, effective treatment or cure for coronavirus disease 2019 (COVID‑19), the disease caused by the SARS-CoV-2 virus. One year into the pandemic, highly effective vaccines have now been introduced and are beginning to slow the spread of SARS-CoV-2; however, for those awaiting vaccination, as well as for the estimated millions of immunocompromised persons who are unlikely to respond robustly to vaccination, treatment remains important. Thus, the lack of progress developing effective treatments means that the cornerstone of management of COVID‑19 has been supportive care, which includes treatment to relieve symptoms, fluid therapy, oxygen support and prone positioning as needed, and medications or devices to support other affected vital organs.

Surgisphere is an American healthcare analytics company established in 2008 by Sapan Desai. Originally a textbook marketing company, it came under scrutiny in May 2020 after it had provided large datasets of COVID-19 patients which were subsequently found to be extremely unreliable. The questionable data was used in studies published in The Lancet and The New England Journal of Medicine in May 2020, suggesting that COVID-19 patients on hydroxychloroquine had a "significantly higher risk of death." In light of these studies, the World Health Organization decided to temporarily halt global trials of the drug hydroxychloroquine to treat COVID-19. After the studies were retracted, the WHO trials were resumed.

RECOVERY Trial Test of existing medicines on COVID-19

The Randomised Evaluation of COVID-19 Therapy is a large-enrollment clinical trial of possible treatments for people in the United Kingdom admitted to hospital with severe COVID-19 infection. The trial was later expanded to Indonesia, Nepal and Vietnam. The trial has tested ten interventions on adults: eight repurposed drugs, one newly developed drug and convalescent plasma.

Adaptive design (medicine)

In an adaptive design of a clinical trial, the parameters and conduct of the trial for a candidate drug or vaccine may be changed based on an interim analysis. Adaptive design typically involves advanced statistics to interpret a clinical trial endpoint.

Sir Martin Jonathan Landray is a British physician, epidemiologist and data scientist who serves as a Professor of Medicine & Epidemiology at the University of Oxford. Landray designs, conducts and analyses large-scale randomised control trials; including practice-changing international trials that have recruited over 100,000 individuals. Landray previously led the health informatics team that enabled the collection and management of data for the UK Biobank on over half a million people.

Bamlanivimab is a monoclonal antibody developed by AbCellera Biologics and Eli Lilly as a treatment for COVID-19. The medication was granted an emergency use authorization (EUA) by the US Food and Drug Administration (FDA) in November 2020, and the EUA was revoked in April 2021.

Chloroquine and hydroxychloroquine during the COVID-19 pandemic

Chloroquine and hydroxychloroquine are anti-malarial medications also used against some auto-immune diseases. Chloroquine, along with hydroxychloroquine, was an early experimental treatment for COVID-19. Neither drug prevents SARS-CoV-2 infection.

Peter Andrew McCullough is an American cardiologist. He was vice chief of internal medicine at Baylor University Medical Center and a professor at Texas A&M University.


  1. 1 2 3 4 "UN health chief announces global 'solidarity trial' to jumpstart search for COVID-19 treatment". United Nations, World Health Organization. 18 March 2020. Retrieved 2 April 2020.
  2. 1 2 3 4 5 6 7 8 9 10 Kupferschmidt, Kai; Cohen, Jon (22 March 2020). "WHO launches global megatrial of the four most promising coronavirus treatments". Science. AAAS. Retrieved 2 April 2020.
  3. 1 2 "'Solidarity' clinical trial for COVID-19 treatment". World Health Organization. Retrieved 22 April 2020.
  4. 1 2 3 4 "Update on WHO Solidarity Trial – Accelerating a safe and effective COVID-19 vaccine". World Health Organization. 27 April 2020. Retrieved 2 May 2020. It is vital that we evaluate as many vaccines as possible as we cannot predict how many will turn out to be viable. To increase the chances of success (given the high level of attrition during vaccine development), we must test all candidate vaccines until they fail. WHO is working to ensure that all of them have the chance of being tested at the initial stage of development. The results for the efficacy of each vaccine are expected within three to six months and this evidence, combined with data on safety, will inform decisions about whether it can be used on a wider scale
  5. 1 2 3 Branswell H (18 March 2020). "WHO to launch multinational trial to jumpstart search for coronavirus drugs". STAT. Retrieved 28 March 2020.
  6. 1 2 3 4 5 "Launch of a European clinical trial against COVID-19". INSERM. 22 March 2020. Retrieved 5 April 2020. The great strength of this trial is its 'adaptive' nature. This means that ineffective experimental treatments can very quickly be dropped and replaced by other molecules that emerge from research efforts. We will therefore be able to make changes in real time, in line with the most recent scientific data, in order to find the best treatment for our patients
  7. Mullard, Asher (18 April 2020). "Flooded by the torrent: the COVID-19 drug pipeline". The Lancet. 395 (10232): 1245–1246. doi:10.1016/S0140-6736(20)30894-1. PMC   7162641 . PMID   32305088.
  8. Miller, Anna Medaris. "A patient in Norway is the first to enroll in a global 'solidarity trial' testing 4 coronavirus treatments". Business Insider. Retrieved 2 April 2020.
  9. 1 2 "Adaptive Designs for Clinical Trials of Drugs and Biologics: Guidance for Industry". US Food and Drug Administration. 1 November 2019. Retrieved 3 April 2020.
  10. 1 2 Pallmann P, Bedding AW, Choodari-Oskooei B, Dimairo M, Flight L, Hampson LV, et al. (February 2018). "Adaptive designs in clinical trials: why use them, and how to run and report them". BMC Medicine. 16 (1): 29. doi:10.1186/s12916-018-1017-7. PMC   5830330 . PMID   29490655.
  11. Kotok A (19 March 2020). "WHO beginning Covid-19 therapy trial". Technology News: Science and Enterprise. Retrieved 7 April 2020.
  12. 1 2 Thomas Mulier (17 June 2020). "Hydroxychloroquine halted in WHO-sponsored COVID-19 trials". Bloomberg. Retrieved 17 June 2020.
  13. "WHO Director-General's opening remarks at the media briefing on COVID-19 - 25 May 2020". World Health Organization. 25 May 2020. Retrieved 27 May 2020.
  14. Maria Cheng, Jamey Keaten (25 May 2020). "WHO pauses hydroxychloroquine coronavirus trial over safety concerns". Global News. The Associated Press. Retrieved 27 May 2020.{{cite news}}: CS1 maint: uses authors parameter (link)
  15. Davey M, Kirchgaessner S, Boseley S (3 June 2020). "Surgisphere: governments and WHO changed Covid-19 policy based on suspect data from tiny US company". The Guardian . Retrieved 4 June 2020.
  16. WHO Solidarity trial consortium (15 October 2020). "Repurposed antiviral drugs for COVID-19–interim WHO SOLIDARITY trial results" (PDF). medRxiv. doi: 10.1101/2020.10.15.20209817 . S2CID   222373329.
  17. 1 2 Jon Cohen, Kai Kupferschmidt (28 October 2020). "The 'very, very bad look' of remdesivir, the first FDA-approved COVID-19 drug". Science. doi:10.1126/science.abf4549. S2CID   228932543.{{cite journal}}: CS1 maint: uses authors parameter (link)
  18. Ali K, Azher T, Baqi M, et al. (19 January 2022). "Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial" (PDF). Canadian Medical Association Journal: cmaj.211698. doi:10.1503/cmaj.211698. ISSN   0820-3946.
  19. "WHO Director-General's opening remarks at the media briefing on COVID-19 - 27 March 2020". United Nations, World Health Organization. Retrieved 2 April 2020.
  20. "Draft landscape of COVID 19 candidate vaccines". World Health Organization. 5 May 2020. Archived from the original on 30 April 2020. Retrieved 9 May 2020.
  21. "An international randomised trial of candidate vaccines against COVID-19". World Health Organization. 19 April 2020. Retrieved 9 May 2020.