Oxford British Bombshell: Hydroxychloroquine Safe, Effective and Affords Modest Protection Against COVID-19, How Many Lives Could Have Been Saved?

121

4 comments

Staff at TrialSite | Quality Journalism

Sep. 13, 2024, 10:00 a.m.

A group of University of Oxford investigators known as the COPCOV Collaborative Group led by Dr. William H. K. Schilling part of the Mahidol Oxford Tropical Medicine Research Unit (MORU) Tropical Health Network, sought to better understand the safety profile of hydroxychloroquine (HCQ). While the drug in a majority of studies chronicled by medical establishments have found the drug to be ineffective in hospitalized patients with COVID-19, what about its safety and efficacy in chemoprevention. A conflict of the evidence emerged however because while randomized controlled trials (RCTs) evidenced no benefit a meta-analysis pointed to possible benefits, yet guidelines around the world recommend against the use of HCQ for COVID-19. TrialSite suggests this drug was politicized potentially due to a confluence of pharmaceutical lobby interests. Regardless, the outcomes show well for HCQ. In this substantially sized (4,652 patient), placebo-controlled, double-blind randomized trial, HCQ and CQ turn out to not only be safe and well tolerated in COVID-19 chemoprevention, but also “evidence of moderate protective benefit in a meta-analysis including this trial and similar RCTs.” This study’s findings mean despite all the turmoil around this drug, the scares as to safety concerns, and the like the drug could have been used as a safe, well-tolerated means of at least moderate protection against SARS-CoV-2. Many lives could have been saved had this outcome come sooner.

The study was just released in September in PLOS Medicine. The study happened thanks to funding from Wellcome Trust via the COVID-19 Therapeutics Accelerator.

The Study

Enter this double-blind, placebo-controlled, randomized trial (NCT04303507) of COVID-19 chemoprevention led by the Oxford University physician-investigators involving the enrollment of healthy adult participants in a healthcare setting, and later from the community across 26 trial sites in 11 countries.

Evaluating the drug used for lupus and rheumatoid arthritis but one that also showed much promise for COVID-19 early on in the pandemic, the COPCOV investigators assessed HCQ in Europe and Africa, and chloroquine (CQ) in Asia, (both base equivalent of 155 mg once daily).

With a protocol primary endpoint of PCR or seroconversion confirmed symptomatic COVID-19, during the 3-month follow-up period. Established secondary and tertiary endpoints were:

Asymptomatic laboratory-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection
Severity of COVID-19 symptoms
All-cause PCR-confirmed symptomatic acute respiratory illness (including SARS-CoV-2 infection)
Participant reported number of workdays lost
Genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity (not reported here)
Health economic analyses of HCQ and CQ prophylaxis on costs and quality of life measures (not reported here)

Findings

The primary and safety analyses were conducted in the intention-to-treat (ITT) population. The intention-to-treat (ITT) population is the group of all patients who were randomized to participate in a clinical trial, regardless of whether they received the intended treatment or completed the trial. The ITT population is used to analyze the outcomes of a trial and is intended to represent what would happen if the treatment were used in real-world clinical practice

Primary Endpoint

A total of 40,000 (20,000 HCQ arm, 20,000 CQ arm) participants was planned for this large global study, however, this was not possible due to a confluence of factors such as protracted delays resulting from controversies over efficacy and adverse events with HCQ use, vaccine rollout in some countries, and other factors.

Between 29 April 2020 and 10 March 2022, Dr. Schilling and colleagues report enrolling 4,652 participants (46% females) (HCQ/CQ n = 2,320; placebo n = 2,332), with a median (IQR) age at 29 (23 to 39) years.

They report that SARS-CoV-2 infections (symptomatic and asymptomatic) occurred in 1,071 (23%) participants. Now, reporting on primary endpoints, the incidence of symptomatic COVID-19 was 240/2,320 in the HCQ/CQ versus 284/2,332 in the placebo arms (risk ratio (RR) 0.85 [95% confidence interval, 0.72 to 1.00; p = 0.05]).

Secondary and Tertiary Endpoints

In reporting the secondary and tertiary endpoints COPCOV principal investigator Schilling and colleagues report asymptomatic SARS-CoV-2 infections occurred in 11.5% of HCQ/CQ recipients and 12.0% of placebo recipients: RR: 0.96 (95% CI, 0.82 to 1.12; p = 0.6).

What about differences in the severity of symptoms between the groups and severe illnesses? There was no report by the authors.

However, “HCQ/CQ chemoprevention was associated with fewer PCR-confirmed all-cause respiratory infections (predominantly SARS-CoV-2): RR 0.61 (95% CI, 0.42 to 0.88; p = 0.009) and fewer days lost to work because of illness: 104 days per 1,000 participants over 90 days (95% CI, 12 to 199 days; p < 0.001).”

Reviewing the meta-analysis of all published pre-exposure RCTs Schilling and colleagues report “that HCQ/CQ prophylaxis provided a moderate protective benefit against symptomatic COVID-19: RR 0.80 (95% CI, 0.71 to 0.91).”

And what about safety concerns? Remember the scare about HCQ and cardiovascular risk during the pandemic. The University of Oxford-led team declared:

“Both drugs were well tolerated with no drug-related serious adverse events (SAEs).”

Final Words

The authors of this important study state that while moving forward it's “unlikely” that CQ or HCQ would be used extensively to protect against COVID-19, “they could have been deployed with benefit earlier, and they might have value in future pandemics.”

This randomized controlled trial is game-changing, a major turnaround from what was incredible politicization involving this drug and COVID-19.

In a telling signal as to what the authors perhaps thought about the conflict, drama and politicization involving this drug early in the pandemic, they concluded: “trials should be facilitated and protected so that evidence is generated rapidly and evidence-based policies can be implemented without delay to allow timely interventions.” How many lives could have been saved?

TrialSite reminds all to search the www.trialsitenews.com platform for evidence of many, quality studies that showed potential safe and efficacious potential with HCQ targeting at least early use prevention against mild to moderate COVID-19.

Limitations

The study turned out substantially smaller than initially planned, plus the relatively low number of PCR-confirmed infections. They also point to a “lower comparative accuracy of serology endpoints (in particular, the adapted dried blood spot method) compared to the PCR endpoint.”

The Principal Investigator

Lead Research/Investigator

William H. K. Schilling, Research Physician, Principal Investigator

Will is a research physician working at the Mahidol Oxford Tropical Medicine Research Unit (MORU), a specialty registrar in Infectious diseases and Microbiology in the UK. He is a DPhil student at the University of Oxford.