Source: Trial Site News
TrialSite’s world survey of the various attempts to stave off and overcome COVID-19 brings the reader back to Zimbabwe, the location of an incredible, underreported scenario urging more attention. TrialSite first covered Zimbabwe when that nation’s medicines regulatory body decided to allow the use of ivermectin for research, and importantly, for research as a care option during the COVID-19 pandemic.
This country experienced a relatively small wave of infections in August 2020 and then a far deadlier, steeper rise in December 2020 into the New Year. With some high profile members of the society (politicians, military leaders, etc.) infected, followed by some deaths, by January 27th the Medicines Control Authority of Zimbabwe (MCAZ) initiated an abrupt turnaround, from what was a resistant position to one of acceptance of Ivermectin.
The results have been astonishing to the say the least. TrialSite’s Daniel O’Connor connected with Dr. Jacqueline (Jackie) Stone, a prominent general practice family physician there as well as proponent of an Ivermectin-based protocol that most certainly appears to have turned back the pandemic’s wrath here—at least for now.
Despite over 50 clinical trials from around the world generating overwhelmingly positive outcomes involving ivermectin, the World Health Organization (WHO) followed the U.S. Food and Drug Administration (FDA) as well as the European Medicines Agency (EMA), recommending against the use of ivermectin due to insufficient data.
Dr. Stone suggests that based on the results of her and colleagues’ case series findings to date (which is now under fast track ethical review to become a retrospective observational study), not using ivermectin would be a violation of both her nation’s constitution, which affords patients the right to emergency care, and importantly, the Helsinki Accords principles—that is that it would be unethical and immoral to deny sick and dying patients a known therapeutic measure evidencing considerable promise of saving lives and alleviating suffering.
A Drug with Such Promise, Yet Rejected
Ivermectin is a safe, Nobel prize winning, World Health Organization (WHO) essential drug extensively used in Africa before COVID to target parasitic conditions such as River Blindness. This drug is known to have antiviral properties against RNA viruses like Yellow Fever, West Nile Virus and HIV. In vitro, it was shown to stop viral replication in Australia in a lab, which TrialSite first shared on April 5, 2020. Since then, sponsors (mostly academic investigator-initiated studies in low-and middle-income countries) have conducted over 50 clinical trials with results overwhelmingly pointing toward positive outcomes.
However, regulators, national apex research institutes, industry and WHO have certainly discounted the positive findings while suggesting these studies are flawed for any number of reasons—from lack of statistical power to too much variability in dosage and overall study design quality. Meanwhile, when these leading organizations do embrace any discussion on the topic, it’s to focus on the one study that shows de minimis results. Ironically, mainstream media such as CNN and New York Times in following what appears to be a playbook, also decided to avoid covering the overwhelmingly positive data story. In the meantime, Facebook, Twitter, YouTube and others continue to censor and punish anyone that dare share positive news about this drug. TrialSite did report that the National Institutes of Health (NIH) plans to study Ivermectin as part of its ACTIV-6 trial.
COVID-19: Ivermectin & the Numbers
However, what’s happened in Zimbabwe frankly should be covered by all the major press interested in real world cases where a country rapidly gets on top of, and beats back, this pathogen.
TrialSite reported that since this nation’s medicinal regulatory body MCAZ embraced a pragmatic and proactive approach to offer the research as a care option targeting COVID-19 using an Ivermectin regimen, the incidence of infection has dramatically waned as evidenced by the overall COVID-19 infection and death numbers.
Made possible by the incessant drive to care for as many patients as possible, Dr. Jackie Stone, a general family medicine provider with the Optimal Health Center in Harare, shared some updates with TrialSite’s founder Daniel O’Connor.
By the end of 2020, a frightening increase in cases was leaving no social cohort untouched in this country of nearly 15 million people. Considered the second wave of the COVID-19 pandemic, a proportionately huge spike in infections and deaths—and in some cases, high profile deaths—had the entire country on edge. Moreover, Zimbabwe overall is a developing country—known as a “low-and middle-income country” (LMIC). This pandemic was to test the readiness and capacity of the healthcare system here in ways not relevant since the HIV/AIDS epidemic.
On December 30, the seven-day average of new infections per day was at 154 cases per day. Just days later, by January 5, that daily figure skyrocketed to 1,365 cases in one day with a reported seven-day average at 553 cases per day. The average daily infection more than tripled in just days.
The situation as we will learn in the interview was bleak, and as a case series evidences here (soon to be converted into a more formal retrospective observational study), an economical, generic drug appears to have saved a lot of lives.
Regulators ‘Buck the Trend’
TrialSite reported on MCAZ’s decision by January 27 to formally authorize the use of the Ivermectin regimen used first in the country by Dr. Stone and colleagues in Harare. What happened next? Nothing short of what can be described as an amazing turnaround.
By February 27, new cases were at 14! As of this writing, the latest number of cases in a day was 12 with a seven-day average of 27 according to data from Johns Hopkins University.
In what Dr. Stone can only attribute to the results of the pervasive use of the ivermectin protocol, the country has completely managed this pandemic in literally a month. Of course, anything can happen—from new variants to a lax in protective measures, leading to yet another spike in infections—but the results of this move by MCAZ could be a model for other LMICs to ascertain.
Introducing Dr. Jackie Stone
A dynamic, outspoken, humorous and engaging physician, Dr. Jackie Stone shared that she’s always had a fascination with science and research while studying at University of Cape town and in London. While she was “meant to be in care,” she had a researcher’s curiosity and thirst for knowledge.
She grew up as a child in Zimbabwe as her father worked in the mining business heading up a group of geologists. She was always fascinated with metals, and the chemistry and associated mechanism of actions studied in science. That intellectual fascination drove this energic and dedicated mind to the study of medicine, but it’s the caring for others that kept her in the clinic over a lab. Over the years of practice, she has learned a lot about practicing in Africa, both in the city and out in rural areas or “the bush.”
Dr. Stone and a number of colleagues here in January formed the Zimbabwe COVID Frontline Clinicians Society to mobilize care givers and other stakeholders to care for patients and overcome the pandemic. What follows are some excerpts from an interview between Dr. Stone and TrialSite’s founder.
Your new organization called ZCFCS sent a letter to the Permanent Secretary of Health there—what was the message?
Well first, ZCFCS was founded from a group of doctors who stood up for patient and doctors rights. We wrote to our Permanent Secretary of Health to express that very important moral.
To quote from this letter written on January 26th 2021 –
“For the past 5 months we have used Ivermectin and adjuvant treatment, either separately or together, alongside the standard of care for our COVID patients. After the first wave, when numbers were low, it was less obvious just how successful this regimen was … but … when the second wave hit in mid December, we found that this protocol was extremely effective. We used far less oxygen, far fewer patients progressed. Some practitioners estimate that they have a less than 1.5% mortality using this combination in a community setting. We believe that the Zimbabwean case fatality rate would have been significantly higher over the last month if we had not been able to use it.“
From your perspective, patients & doctors’ rights matter—don’t they?
Absolutely! We found out about the ongoing Ivermectin studies first and thereafter the FLCCC and Borody protocols, and we adapted them to reflect our local situation. Importantly, we did this to follow our Hippocratic oath. This drug isn’t some experimental treatment with no track record. Rather, its been used for four decades; the safety and dosage profiles and safety thresholds are very known.
I believe in very basic rights that drive the care for patients, and those for the doctor to ensure that they can do what is necessary to appropriately care for our patients.
Under section 76 of our constitution here, every patient has the right not to be refused emergency care. Moreover, for research under the Helsinki Accord, ethics drive physicians’ use of known safe, repurposed therapeutic measures if it offers serious hope of saving lives and alleviating suffering.
When did you first start treating patients with ivermectin?
Again, we serve an outpatient population that represents a majority of the COVID-19 cases. We had been using local approaches, and by August, in collaboration with physicians from South Africa, we started using Ivermectin. Immediately (within a couple days), we noticed positive results with some critical patients in the outpatient setting. Although we run an outpatient facility, many patients were leery of the state-sponsored hospital and visited us.
We were picking up what we could about Ivermectin-based studies, and by the late Fall, we learned of both the FLCCC protocol as well as the triple-therapy Ivermectin-based recommendation from Dr. Thomas Borody, a physician/researcher in Australia. We added these to our own treatment protocols, which had of course evolved with local experience to what we now have today.
But again, once we started including ivermectin in a local protocol back in August, we started with a handful of very sick patients. We noticed something profound almost immediately—they started getting better once on the ivermectin-based regimen.
Can you share more about the protocol?
The protocol may depend on severity, and I give an example of a case I will present at a forthcoming conference. A 25-year-old male in the 5th day of his illness, experienced bilateral pneumonia and positive rapid antigen. He was seen in a GP clinic with no oxygen. In an outpatient setting, we treated the patient with 1) Ivermectin 12mg once daily; 2) Zinc 40mg once daily; 3) Doxycycline 100mg twice daily (for those with high neutrophil count); 4) IONS 20 ml nebulized (until Sats >93%); and 5) Prednisolone 40 mg once daily (CRP>20 and hypoxic).
So by the fourth day, he was well on his way to mend at Sats 97%, Pulse 77, and deemed clinically recovered. This scenario is not uncommon among our patients. Case after case was similar, and in those patients with just mild symptoms (the great majority of cases), the clinical benefit has been material.
With growing success with patients, why were at least some in medical associations so publicly against your method care for patients?
There was quite a bit of resistance to trying something new from at least some resistant-minded people. I think we have seen this in many countries: a resistance to anything that’s not directed by the WHO, for example.
While this led to some challenges (I was even detained!), we ultimately demonstrated that this approach was (and is) working, and that’s what we are talking about here—helping, alleviate suffering, and reducing the patient death rate during the pandemic.
But the drug wasn’t registered for this particular use or indication and yet we were in fact using it in the clinic, as a form of emergency use.
The rules are important as are the flexible guidelines long used by doctors to improvise with existing, well known therapies, using their best judgement along with full patient consent—a fundamental tenet of any successful healthcare.
Detained! Can you share a little more?
You know, it’s really trivial and insignificant at this point as compared to the magnitude of the pandemic and the collective mission to care for patients and save lives. We started a movement here caring for the ill back in August yet it wasn’t authorized formally; it was done as doctors have done many times before, improvising and adjusting out in the clinic, which over time represents a form of innovation.
But here in Zimbabwe, someone high up in one of the medical associations called and complained but ultimately it all sorted itself out. In the end, we have cared for thousands of patients here, from those at the top of society down to the poorest of the poor. And the results are there.
Our goal is to care for people, save lives, and if we find something that we know is safe and works, we most certainly will pursue it and ask for forgiveness later. That’s our Hippocratic oath.
TrialSite notes that interestingly the Chinese press covered a negative story centering on Dr. Stone. Ultimately, TrialSite learned that Dr. Stone and colleagues’ efforts saved a lot of lives. They treated influential people in the military and government, which could have influenced the opening up to off-label use of the FDA approved drug.
What data do you have evidencing that ivermectin is working?
First, we have the result of our case series involving a few hundred patients showing overwhelmingly positive outcomes.
And as we discussed, the death rate by Jan 25 (the day before MCAZ’s change to accepting of ivermectin) was 70 for that day and a seven-day average of 43 per day. On January 27, MCAZ formally authorized the use of ivermectin and, as your last article reveals, data of skyrocketing sales indicated widespread use. Now the overall rates were headed up and there was no clear indication that the country had reached the apex peak. But intensive use of ivermectin followed those weeks after. (Note, this was reported by TrialSite on February 16).
By February 26, the there were 0 deaths reported across the country and the seven day average was 4 per day, a dramatic turnaround, and overwhelmingly positive direction for this country of nearly 15 million people.
So what about some specific data points?
We have demonstrated, via actual real-world case series, the tremendous turnaround in infection and death rates since the country’s regulator allowed usage. In the state hospitals in what are called “Red Zones” or units with severe COVID-19 cases, Ivermectin isn’t used and the data indicates that the mortality rate for those COVID-19 patients has been 34.40%. Meanwhile, in the outpatient environment where we utilized the Ivermectin and triple adjuvant therapy for those patients in severe condition (PO2 between 39% and 90%), the mortality rate has been 3.80%. We have the documentation to share for those that are interested.
You know, when the second wave hit in January, we were running out of hospital beds. Many patients came to our clinic. In the case series, we had 104 patients in moderate-to-severe condition. In a state where they should be hospitalized, again the capacity may have not been there and/or in some cases, people were concerned that there was no care occurring in the hospital setting.
So this class of patient should be hospitalized, and in a hospitalized setting, the COVID-19 death rate here is 20%. In our outpatient setting with the treatment regimen, we lost only 1 out of 104 patients—a remarkable difference, but I still mourn the life lost.
Did you document case series? Will an observational study result?
Yes, we have, but admittedly it’s been difficult to do so with the rigor one would seek to achieve, while in parallel providing the care. That’s why we have a retrospective observational study protocol under fast track ethical review now. As conditions improve, we can concentrate some time and resources to the study data. Then we will incorporate all of our data and associated documentation from the case series and produce an important study.
It’s essential to note for the TrialSite audience that in many LMICs, its difficult to set up large, formal, randomized controlled trials right as the pandemic rages, as clinicians must first and foremost care for patients. I most certainly wish we would have more funds, resources and the like for more extensive research as well.
But I can report that the ethical approval for a retrospective, observational study is now under a fast track process here in Zimbabwe. If that study shows that Ivermectin is safe and effective in the Zimbabwean context, we will certainly have a moral obligation to use what is available and affordable to the patients we serve.
What’s your position on the recent WHO recommendations?
When WHO came out with its recommendations against Ivermectin, we simply did not understand why they would not support the widespread use of such an affordable drug with this safety profile and international data supporting evidence for large reductions in mortality.
WHO, in the past, has done so much good in this country with other pandemics and epidemics, such as HIV and Malaria, not to mention their work in Maternal and Child Health and other areas. But this time, they seem to not understand the reality of what is happening on the ground in Low Middle Income Countries. We do not have the time, funds or resources for the magnitude of the research they are calling for before a third wave breaks.
At this point, continuing the use of Ivermectin has proven safe and we see no reason to stop this drug, which seems to have not only inhibited our second wave but so far prevented a third one.
In addition, our malaria deaths have come down dramatically as Ivermectin stops mosquitos from being able to reproduce. Mortality from more than one infectious disease has come down dramatically with this treatment. We feel it is unethical to stop it.