Contrary to Senator Paul Rand’s infamous angry rant on ivermectin, researchers have just released the results from the largest US study to date on the repurposed COVID drug.
The 2015 Nobel Prize winning anti-parasite medicine, one of several made famous during the Trump administration, was examined alongside the SSRI fluvoxamine – commonly used to treat OCD and depression – and the diabetic drug metformin. Both have also been associated with experimental COVID treatment.
In the study, published August 18th in The New England Journal of Medicine, researchers from the University of Minnesota tested the repurposed drugs as early intervention treatments in a double-blind, randomised placebo-controlled trial across 1323 at-risk, overweight COVID patients.
Lead authors, Dr David Boulware and Professor Thomas Murray, explained that none of the drugs had a significant effect on four severe COVID outcomes combined.
“In this placebo-controlled clinical trial of metformin, ivermectin, and fluvoxamine for early outpatient treatment of COVID, none of the three drugs had a significant effect on the composite primary end point of hypoxemia, emergency department visit, hospitalization, or death,” they said.
“We did not find evidence that fluvoxamine at a low dose of 50 mg twice daily prevented a primary event in this population… [though] the dose may need to be higher to produce an effect, especially in patients who are overweight or have obesity.
“Likewise, we did not find evidence that ivermectin prevented a primary event in this population of U.S. adults who were 30 years of age or older and who had overweight or obesity.
“Because a previous randomized trial of ivermectin at a dose of 300 μg per kilogram per day did not show any significant effect, we chose a higher dose, a median of 430 μg per kilogram (range, 390 to 470 μg per kilogram) per day.”
However, the study did find that metformin showed a ‘possible’ association with lower hospitalisations, ER visits, and death, though it was not strong enough for the team to make a definitive conclusion without more research.
“The proposed mechanisms of action against COVID for metformin include anti-inflammatory and antiviral activity, and the prevention of hyperglycemia during acute illness: further investigation is needed to determine whether any of these proposed mechanisms has any clinically meaningful activity in the treatment of COVID,” Professor Murray said.
“A higher dose of metformin may not improve anti-inflammatory actions, as suggested in a recent study of macular degeneration. Also, immediate-release metformin may have higher peak systemic exposure than the extended-release formulation, which may be relevant in COVID infection.”
The authors explained that the patients started metformin at a dose of 1500 mg per day without dose adjustment, which may have caused side effects and discontinuations, but in the per-protocol analysis, hospitalization occurred in 8 of 168 patients (4.8%) in the metformin group and in 14 of 179 patients (7.8%) in the control group.
Ivermectin first made COVID headlines alongside hydroxychloroquine on 1 December 2020, during an interview with one of Trump’s doctors by Fox News host Laura Ingraham, and was featured the following week in a controversial hearing by then-Senate Homeland Security Committee Chairman Ron Johnson.
When Johnson claimed that information on these drugs was being censored, a statement repeated by Ingraham, they became instantly politicised and were seized upon by elements of the right associated with the anti-vaccine movement.
Trump stalwart, Republican Senator Paul Rand, infamously blamed scientists for not investigating ivermectin in August 2021, stating that, “the hatred for Trump deranged these people so much, that they’re unwilling to objectively study it.”
That week US health authorities reported a huge jump in the number of calls for ivermectin poisoning with the Oregon Poison Centre, in the Senator’s home state of Kentucky, reporting six hospitalisations.
The issue of disinformation was inevitable, with ivermectin plagued by scientific studies that were found to have falsified data, such as an Egyptian study published in November 2020, which had provided the main basis for initial support by doctors.
The research was retracted in July 2021 after it was discovered that results had been plagiarised, patient records had been duplicated and, in some cases, the participants had either never existed or were already dead.
The latest, reputable findings echo those of a Brazilian study of 3515 patients from March 2022, Effect of Early Treatment with Ivermectin among Patients with Covid-19, which concluded that treatment with ivermectin had no effect on the number of patients admitted to hospital due to the progression of COVID, and no effect on the prolonged emergency department observation times for outpatients with an early diagnosis of disease.
Similarly, results from a clinical trial in Malaysia, published in February in JAMA Internal Medicine, found that ivermectin failed to stop severe disease developing in high-risk people with mild to moderate COVID. The authors said their study of 490 patients across 20 hospitals did not support the use of ivermectin for patients with the virus.