Public health emergency SOLIDARITY trial of treatments for COVID-19 infection in hospitalized patients
| ISRCTN | ISRCTN83971151 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN83971151 |
| Secondary identifying numbers | 0003361 |
- Submission date
- 25/03/2020
- Registration date
- 25/03/2020
- Last edited
- 30/09/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.
In 2020, the virus has spread to many countries around the world and neither a vaccine against the virus or specific treatment for COVID-19 has yet been developed. As of March 2020, it is advised that people minimize travel and social contact, and regularly wash their hands to reduce the spread of the virus.
Groups who are at a higher risk from infection with the virus, and therefore of developing COVID-19, include people aged over 70 years, people who have long-term health conditions (such as asthma or diabetes), people who have a weakened immune system and people who are pregnant. People in these groups, and people who might come into contact with them, can reduce this risk by following the up-to-date advice to reduce the spread of the virus.
There are currently no available vaccines or treatments for COVID-19. Although there have been some suggestions for untested treatments that could be added to the usual care in hospitals, none is known to help. The World Health Organization (WHO) is, therefore, organizing a study in many countries in which some of these untested treatments are compared with each other, to discover whether any do help. The study treatments are remdesivir, chloroquine or hydroxychloroquine, lopinavir plus ritonavir, and interferon-beta. Some are given as daily pills, and some as daily injections.
Who can participate?
Adults (aged over 18 years) hospitalized with definite COVID-19 and not already receiving any of the study drugs. Patients invited to join the study will be those who are admitted to a collaborating hospital. It is not possible for people to volunteer themselves or their relatives to participate.
What does the study involve?
Patients diagnosed with COVID-19 and who have consented to be part of the study will be randomly allocated to receive either local standard care alone or local standard care and one of a list of study drugs. During the study, some treatments may get removed from this list, and others may be added to it. Each patient will only receive one of the treatments.
The patients will be followed up for the entire length of their hospital stay. Death from any cause will be recorded and this will be the main result used to determine whether a drug is effective. Length of hospital stay and time to first receiving ventilation (or intensive care) will also be recorded and used to determine the drug's effectiveness.
What are the possible benefits and risks of participating?
All of the drugs tested in this study have been shown to be reasonably safe. Other than remdesivir the study drugs are used routinely to treat other conditions. All participants will receive the usual care for people with COVID-19 in each location as well as the study drug.
There are known side effects to each of the study medications. It is possible that unexpected serious side effects may occur as with any clinical trial of medicines. It is also possible that treatment with one or more of the test drugs worsens COVID-19 and increases the risk of severe illness or death.
It is possible that one or more of the drugs may reduce the severity of COVID-19, reduce need for ventilation, and reduce the risk of death.
Where is the study run from?
World Health Organization Headquarters (Switzerland)
When is the study starting and how long is it expected to run for?
March 2020 to March 2021
Who is funding the study?
Multiple funders including the World Health Organization (Switzerland)
Who is the main contact?
Dr Ana Maria Henao Restrepo, henaorestrepoa@who.int
Dr Vasee Moorthy, moorthyv@who.int
Dr Marie-Pierre Preziosi, preziosim@who.int
Contact information
Scientific
Medical Officer, HQ/RDB R&D Blue Print
(HQ/HEO/RDB)
World Health Organization HQ
Geneva
1211
Switzerland
 ORCID ID |
0000-0001-9910-7999 |
|---|---|
| Phone | +41 795130039 |
| henaorestrepoa@who.int |
Scientific
Co-Lead, R&D Blueprint for Action to Prevent Epidemics
World Health Organization HQ
Geneva
1211
Switzerland
| ORCID ID |
0000-0002-6535-2854 |
|---|---|
| Phone | +41 227914760 |
| moorthyv@who.int |
Scientific
Co-Lead, R&D Blueprint for Action to Prevent Epidemics
World Health Organization HQ
Geneva
1211
Switzerland
| ORCID ID |
0000-0002-9025-6493 |
|---|---|
| Phone | +41 227913744 |
| preziosim@who.int |
Study information
| Study design | Open-label randomized multicountry clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | An international randomized trial of additional treatments for COVID-19 in hospitalized patients who are all receiving the local standard of care |
| Study acronym | SOLIDARITY |
| Study hypothesis | The addition of treatment to the local standard of care reduces all-cause mortality in COVID-19 patients compared to the local standard of care alone. |
| Ethics approval(s) | Approved 04/05/2020, WHO Research Ethics Review Committee (20, Avenue Appia – Ch-1211 Geneva 27 – Switzerland; +41 227573052; ercsec@who.int), ref: ERC.0003361 |
| Condition | COVID-19 (SARS-CoV-2 infection) |
| Intervention | Adults (aged ≥18 years) recently hospitalized, or already in the hospital, with definite COVID-19 and, in the view of the responsible doctor, no contra-indication to any of the study drugs will be randomly allocated between five groups: 1. Local standard of care alone OR local standard of care plus one of 2. Remdesivir (daily infusion for 10 days) 3. Chloroquine or hydroxychloroquine (two oral loading doses, then orally twice daily for 10 days) 4. Lopinavir + ritonavir (orally twice daily for 14 days) 5. Lopinavir + ritonavir ((orally twice daily for 14 days) plus interferon-beta (daily injection for 6 days) Follow-up is until death or discharge from hospital. Randomization is performed at one central global location through an online portal. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Remdesivir, chloroquine or hydroxychloroquine, lopinavir + ritonavir (Kaletra), interferon-beta |
| Primary outcome measure | All-cause mortality, subdivided by the severity of disease at the time of randomization, measured using patient records throughout the study |
| Secondary outcome measures | Measured using patient records: 1. Duration of hospital stay (hours) 2. Time to first receiving ventilation (or intensive care) (hours) |
| Overall study start date | 01/03/2020 |
| Overall study end date | 25/03/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | No specific sample size is specified in this public health emergency core protocol. It is anticipated that at least several thousand patients will be recruited into the trial. |
| Total final enrolment | 11266 |
| Participant inclusion criteria | 1. Adults (aged ≥18 years) hospitalized with definite COVID-19 2. Not already receiving any of the study drugs 3. Without known allergy or contraindications to any of them (in the view of the physician responsible for their care) 4. Without anticipated transfer within 72 h to a non-study hospital Patients invited to join the study will be those who are admitted to a collaborating hospital; no wider recruitment efforts are expected |
| Participant exclusion criteria | Current exclusion criteria as of 21/04/2020: 1. Any of the available study drugs are contra-indicated (e.g. because of patient characteristics, chronic liver or heart disease, or some concurrent medication) 2. Declined to participate in the study Previous exclusion criteria: 1. Any of the available study drugs are contra-indicated (e.g. because of patient characteristics, chronic liver or heart disease, or some concurrent medication) 2. Pregnant 3. Declined to participate in the study |
| Recruitment start date | 26/03/2020 |
| Recruitment end date | 28/02/2021 |
Locations
Countries of recruitment
- Argentina
- Brazil
- Canada
- Germany
- Honduras
- India
- Indonesia
- Iran
- Ireland
- Israel
- Italy
- Kenya
- Lebanon
- Malaysia
- Norway
- Peru
- Philippines
- Qatar
- Saudi Arabia
- South Africa
- Spain
- Switzerland
- Thailand
Study participating centre
Switzerland
Sponsor information
Government
Avenue Appia 20
Geneva
1211
Switzerland
| Phone | +41 22712111 |
|---|---|
| henaorestrepoa@who.int | |
| Website | https://www.who.int |
"ROR" |
https://ror.org/01f80g185 |
Funders
Funder type
Research organisation
Private sector organisation / International organizations
- Alternative name(s)
- منظمة الصحة العالمية, 世界卫生组织, Всемирная организация здравоохранения, Organisation mondiale de la Santé, Organización Mundial de la Salud, WHO, 世卫组织, ВОЗ, OMS
- Location
- Switzerland
Results and Publications
| Intention to publish date | 31/12/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | This international collaboration is co-ordinated through the World Health Organization, which is also a sponsor of the trial. Any wholly reliable interim findings will be disseminated rapidly by the WHO. There will be group authorship recognizing the contribution of all national and local investigators and guided by the International Committee of Medical Journal Editors (ICMJE) recommendations. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Interim results article | interim results in preprint | 15/10/2020 | 19/10/2020 | Yes | No |
| Results article | interim results for remdesivir, hydroxychloroquine, lopinavir and interferon | 11/02/2021 | 25/03/2021 | Yes | No |
| Results article | final results and updated meta-analyses | 02/05/2022 | 06/05/2022 | Yes | No |
| Protocol file | version 10 | 22/03/2020 | 30/09/2022 | No | No |
Additional files
Editorial Notes
30/09/2022: Uploaded protocol (not peer reviewed).
06/05/2022: Publication reference added.
25/03/2021: Publication reference added.
19/10/2020: The following changes have been made:
1. Preprint reference added.
2. The final enrolment number has been added from the reference.
27/07/2020: The ethics approval was added.
21/04/2020: The following changes have been made:
1. Honduras, India, Ireland, Israel, Italy, Kenya, Lebanon, Malaysia, Philippines and Saudi Arabia have been added to the locations of recruitment.
2. The participant exclusion criteria have been changed.
02/04/2020: The trial website has been removed.
30/03/2020: Internal review.
25/03/2020: Trial’s existence confirmed by the WHO.
