E-DRUG: WHO Solidarity clinical trial for covid-19 treatments
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Dear E-druggers,
We are being overwhelmed by information on what works to 'treat' COVID-19.
Not least has the US been quick in going public with preliminary data and
drug companies are probably happy for that. One worry now is that the
European Medicines Agency will follow US FDA and approve remdesivir too
early. Some research is getting less attention even if it aims to collect enough data to draw conclusions.
One of them is the WHO supported Solidarity trial:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-resea
rch-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-tr
eatments
It was launched by WHO Director-General's opening remarks at the media
briefing on COVID-19 on 18 March 2020 and I've posted information from the
website below with some comments from me in brackets in the next paragraph.
"Solidarity" is an international clinical trial to help find an effective
treatment for COVID-19, launched by the World Health Organization and
partners.
The Solidarity Trial will compare four treatment options against standard of
care, to assess their relative effectiveness against COVID-19. By enrolling
patients in multiple countries, the Solidarity Trial aims to rapidly
discover whether any of the drugs slow disease progression or improve
survival. Other drugs can be added based on emerging evidence. Until there
is sufficient evidence, WHO cautions against physicians and medical
associations recommending or administering these unproven treatments to
patients with COVID-19 or people self-medicating with them. WHO is concerned
by reports of individuals self-medicating with chloroquine and causing
themselves serious harm. WHO guidance on compassionate use can be found
here.
https://www.who.int/news-room/commentaries/detail/off-label-use-of-medicines-for-covid-19
[The drugs chosen to be tested are listed below. In addition, countries may
choose to add other treatments. 14 countries now participate in a multi-country trial whose objectives are to measure need for respirator treatment and mortality compared to standard treatment in intensive care. This is a different objective than e.g. the recent Gilead sponsored remdesivir trial which treated hospitalised patients with a 10-days course of remdesivir
https://pharmaphorum.com/news/first-study-of-gileads-remdesivir-in-covid-19
-reveals-little/
So it is important to look at the objective(s) of different clinical trials when evaluating them. Unfortunately, China, Japan, UK and US do not participate.
The trial results - the aim was to get first results in June - might therefore take longer. The person in charge of coordination is the director of the Norwegian Research Council, John-Arne Rottingen and there is an international steering committee. ]
Rationale for the Solidarity trial
The pressure COVID-19 puts on health systems means that WHO considered the
need for speed and scale in the trial. While randomized clinical trials normally take years to design and conduct, the Solidarity Trial will reduce the time taken by 80%. Enrolling patients in one single randomized trial will help facilitate the rapid worldwide comparison of unproven treatments. This will overcome the risk of multiple small trials not generating the strong evidence needed to determine the relative effectiveness of potential treatments.
Participation in Solidarity
The Solidarity Trial provides simplified procedures to enable even
overloaded hospitals to participate, with no paperwork required. As of April
21, 2020, over 100 countries are working together to find effective
therapeutics as soon as possible, via the trial. The greater the number of
participating countries, the faster results will be generated. WHO is
facilitating access to thousands of treatment courses for the trial through
donations from a number of manufacturers. WHO is also inviting developers
and companies to collaborate.
Based on evidence from laboratory, animal and clinical studies, the
following treatment options were selected: Remdesivir; Lopinavir/Ritonavir;
Lopinavir/Ritonavir with Interferon beta-1a; and Chloroquine or Hydroxychloroquine.
Remdesivir was previously tested as an Ebola treatment.
It has generated promising results in animal studies for Middle East
Respiratory Syndrome (MERS-CoV) and severe acute respiratory syndrome
(SARS), which are also caused by coronaviruses, suggesting it may have some
effect in patients with COVID-19.
Lopinavir/Ritonavir is a licensed treatment for HIV. Evidence for COVID-19, MERS and SARS is yet to show whether it can improve clinical outcomes or prevent infection. This trial aims to identify and confirm any benefit for COVID-19 patients. While there are indications from laboratory experiments that this combination may be effective against COVID-19, studies done so far in COVID-19 patients have
been inconclusive.
Interferon beta-1a is used to treat multiple sclerosis. Chloroquine and
hydroxychloroquine are very closely related and used to treat malaria and
rheumatology conditions respectively. In China and France, small studies
provided some indications of possible benefit of chloroquine phosphate
against pneumonia caused by COVID-19 but need confirmation through
randomized trials.
Kirsten Myhr, MScPharm, MPH
Kongsberg, Norway
phone: +47 41638747
myhr@online.no