The SAIVE trial for prevention of COVID-19

Professor Colleen Aldous is a research professor at in the School of Clinical Medicine at the University of Kwazulu-Natal in South Africa. She recently described the SAIVE trial of prophylactic ivermectin for covid-19 as the “best quality RCT we have yet seen published on ivermectin”. In this series of short videos, she explains what makes the SAIVE trial so good and explores the wider issue of how evidence for effectiveness of repurposed drugs, such as ivermectin, could be evaluated in a timely manner.

What makes the SAIVE study so good?

Professor Aldous has frequently advocated the use of ivermectin for the treatment and prophylaxis of SARS-CoV-2 infection (covid-19) and has worked closely with front-line physicians in this field.  She explains that participants in the SAIVE trial were unvaccinated and had been exposed to a person with PCR-confirmed SARS-CoV-2 infection. The dosing of ivermectin – 200 micrograms per kilogram on the first day and 100 micrograms per kilogram for the next 27 days – was designed to emulate the slow-release injectable product that Medincell is developing. The results showed that there was a 72 per cent reduction in infections in participants who received ivermectin.

https://youtu.be/uzpxNfb2YZI

Ivermectin – is it safe and effective?

Ivermectin has two particularly important mechanisms of action in covid-19; it kills the virus and it prevents or reverses haemagglutination that otherwise leads to micro-clotting. “I would say that the best window to use ivermectin is at the beginning of the viral infection – [at the] infective stage”, she says. Had the drug been used in this way then there could have been a 58-59 per cent reduction in mortality, she notes.

https://youtu.be/tsm5wYmbpM0

TOGETHER trial shows positive effect for ivermectin

The TOGETHER trial, widely reported as showing that ivermectin was not effective in covid-19, actually showed a 58-59 percent reduction in mortality in the ivermectin treated group. Furthermore, the ivermectin was given “when people had at least seven days …. of being symptomatic; their viral phase had passed. That window where ivermectin would have done its best work was gone”, says Professor Aldous. Despite this late administration of the drug there was still a positive effect for ivermectin, she emphasises.

https://youtu.be/urfghlGVRK8

Addressing the totality of evidence for ivermectin

Randomised controlled trials (RCTs) alone are not the most efficient way to identify effective treatments using repurposed drugs, argues Professor Aldous. What is needed is a way to evaluate the ‘totality of evidence’. This would take into account laboratory studies, case reports, observational studies and RCTs, she says. It would also be in line with David Sackett’s original conception of evidence-base medicine, she notes.

https://youtu.be/fK1ocsEjHRg

How the totality of evidence (for ivermectin) informs clinical practice

The evidence supporting the use of ivermectin for covid-19 came together from a variety of sources to tell a compelling story. Laboratory studies showed that it was virucidal in vitro. Frontline clinicians in Zimbabwe, California and Nigeria all reported similar results – rapid recovery from oxygen desaturation. Further laboratory studies demonstrated the reversal of covid-induced haemagglutination and the SAIVE RCT now provides robust evidence that infection can be prevented.

https://youtu.be/GCcfOSgOFU4

Read and watch the full series on our website or on YouTube.