‘HOPE’ for the future - Showing the way forward for clinical trials in challenging circumstances
The largest study to test hydroxychloroquine (HCQ) as a preventative medicine for COVID-19 in a low- and middle-income setting, Hydroxychloroquine Prophylaxis Evaluation (HOPE), has been published in the BMJ Open journal.
The George Institute’s team, led by Dr Bharath Kumar, Prof Vivekanand Jha and Prof. Bala Venkatesh, directed this trial in India. The study was planned and conducted on the background of early reports during the pandemic suggesting that the use of HCQ could provide an effective preventive shield against the SARS-Cov2 infection for healthcare workers (HCWs) on the frontlines at high risk of contracting the infection.
The easy availability, lower cost, and proven safety track record of HCQ when used for other clinical indications provided additional rationale for embarking on a clinical trial to test the effectiveness of this drug in preventing COVID-19. The trial assumed particular importance for India due to the widespread shortage of personal protective equipment for HCWs in the early stages of the pandemic and the expected delays in the commencement of vaccination. In addition, the Indian Council of Medical Research (ICMR) at that point recommended the use of HCQ as a prophylactic while advocating for clinical trials.
HOPE involved dividing the screened participants (healthcare frontline workers who were treating COVID-19 patients in hospitals, clinics, etc.) in two groups. One of the groups received HCQ in doses recommended by the Indian Medical Research Council – 800 mg on the first day followed by 400 mg each week for next 12 weeks. The follow-up went for 6 months, making this the longest follow-up duration among hydroxychloroquine-related trials.
The trial, however, had to be halted early for futility as vaccine rollout in India began (for health care workers could take the vaccine for protection) and due to the adverse publicity surrounding the use of this drug. Considering the unstated implications and efficacy of HCQ, the ICMR raised a warning against its excessive use by healthcare workers as a preventative medicine for COVID-19 and issued an advisory towards the same. The researchers were unable to make any definitive conclusions because they could not exclude either harmful or beneficial effects of the drug.
Despite the premature stop for futility, the trial yielded several positive dividends. It demonstrated how multicentric academic clinical research could be undertaken in the midst of a once-in-a-lifetime pandemic and crucially, created important clinical trial capacity at participating centres. Additionally, there were regulatory, operational, and funding barriers to overcome. The study investigators summarised these issues in a comment article - "Challenges in operationalising clinical trials in India during the COVID-19 pandemic" - published in the Lancet Global Health and presented solutions that would facilitate the conduct of clinical trials in a situation like the pandemic.
"It is noteworthy that HOPE was designed and conducted with the highest standards even during one of the worst pandemics we have ever seen. The fact that we were able to enrol over 400 participants during the peak pandemic times speaks volumes about the effort which underwent." says Prof Vivekanand Jha, the Executive Director of The George Institute, India.
The team focused on compliance with the intervention, data quality, and participant safety and was even able to achieve a 99% follow-up response rate.
It has paved the way for further collaborative efforts and underscored the importance of timely research, fostered future research, and set the stage for many more trials in challenging times.
“Bringing nine centres across India together to collaborate and create research capacity is evidence of our ability to bring sustainable positive change under challenging circumstances." emphasises the lead author of the study Dr Bharath Kumar, Intensivist at Apollo Hospital, Chennai & Honorary Fellow, The George Institute, India
The George Institute for Global Health acted as a Sponsor and coordinating centre and facilitated the conduct of the HOPE trial in India. The results of the trial are consistent with previously published data from other settings. It was published by The BMJ open, and the full paper can be accessed here.