The WHO solidarity trial consortium, which is composed of an international team of physicians finally published the results of the clinical trial on Med Archive (MedRxiv) last week. The goal of the WHO solidarity trial was to evaluate the efficacy of four treatments - Remdesivir, Hydroxychloroquine, Lopinavir (fixed-dose combination with Ritonavir) and Interferon-β1a in improving various outcomes of hospitalized COVID19 patients. The outcomes that were evaluation in the trial were 1. Mortality; 2. Need for assisted ventilation; 3. Duration of hospital stay. The study was mostly funded by the participating countries and WHO covered all other study costs (received no external funding).
In March 2020, the WHO began to organize a large, multi-country randomized trial among hospital in-patients with COVID19. The idea here is that COVID19 patients in hospitals will most likely be those suffering and presenting moderate to severe symptoms and it is also simpler to evaluation and observe patient outcomes when participants are in-facility. The study concluded in October 2020.
I am sure by now, many of you have seen/ heard about these four controversial drugs used in treating COVID19. Before we continue, here is a quick rundown of the four drugs tested in this study to refresh your memory:
Study design
In 405 hospitals in 30 countries 11,266 adults were randomized, with 2750 allocated Remdesivir, 954 Hydroxychloroquine, 1411 Lopinavir, 651 Interferon plus Lopinavir, 1412 only Interferon, and 4088 no study drug. Placebos were not used.
Demography of participants
The dose and delivery of the drugs are as follows:
Results
1. No study drug had any definite effect on mortality.
Death rate ratios (drug v.s. control):
Remdesivir RR=0.95
Hydroxychloroquine RR=1.19
Lopinavir RR=1.00
Interferon RR=1.16
What these numbers mean is that essentially, there are no significant differences between the mortality among patient treated with and without the drug (RR=1 means no difference at all).
2. No drugs resulted in an increase in recovery rate
3. None of the drugs were able to reduce the need to ventilate COVID19 patients that were not ventilated at the start of the study.
4. The proportions still hospitalized at day 7 (of treatment), study drug vs control, remains similar to no drug controls.
The results presented in this study is clear and concise. In conclusion, Remdesivir, Hydroxychloroquine, Lopinavir and Interferon appeared to have little or no effect on hospitalized COVID-19 patients, as indicated by the parameters evaluated - overall mortality, initiation of ventilation and duration of hospital stay.
Some limitations to take note
This study, once again, effectively addressed our suspicion (based on other studies published over the past months) that these four repurposed drugs do not improve mortality, ventilation and hospitalization of moderate-severe COVID19 patients. However, it is important to acknowledge that this study does not address other outcomes like disease severity, symptom alleviation, immune responses and immunity and immunization.
Also, the study did not report on any adverse side effects (if any) experienced by participants who received the study drugs. The authors did mention that the drug treatments did not pose any hazards by way of mortality but there were no mentions of harmful side effects.
Lastly, the authors acknowledged that that delivery methods of Interferon (i.e. subcutaneous, intravenous) may influence pharmacokinetics of the drug but the clinical relevance of that is not studied in this trial.
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