No evidence budesonide, clarithromycin, and aspirin combination is “silver bullet” for COVID-19, contrary to Texas doctor’s claim

In a 30 January 2024 episode of the Big Honker Podcast, Texas physician Richard Bartlett claimed that he had developed a “silver bullet” treatment for COVID-19 comprising budesonide, clarithromycin, and aspirin. The podcast’s co-host, Andy Shaver, claimed that this treatment was “silenced”. A Facebook reel containing these claims received more than 180,000 views at the time of this review’s publication.

Bartlett, who ran for Congress as a Republican in 2019, notably appeared on the show America Can We Talk in 2020, in which he discussed his successful experience using this combination of drugs to treat COVID-19. He also held a press conference in June 2020, asserting that his patients had “a 100% survival rate. I don’t even know how many I’ve treated…dozens. I have 14 that I’m treating now”.

He also said at that time that he was writing a paper to submit to medical journals. A search on PubMed, a repository of scientific studies maintained by the U.S. Library of Medicine, turned up no published studies or randomized clinical trials related to Bartlett’s “silver bullet” under his name.

As the above indicates, the claim that Bartlett was “silenced” doesn’t stand up to scrutiny. His claim of finding a “silver bullet” for COVID-19 was covered by media outlets in 2020, including Fortune, The Texan, and a Texas CBS affiliate CBS7. Moreover, his claim went viral and was covered by fact-checking organizations FactCheck.org and AFP.

These media reports also illustrate that Bartlett mainly substantiated his claims by using anecdotal experience from treating COVID-19 patients rather than with published studies or randomized clinical trials.

More importantly, the studies that have been published so far don’t demonstrate that this combination of drugs is effective against COVID-19. We explain below.

Scientific studies to date don’t support using budesonide, clarithromycin, or aspirin as to treat COVID-19

Budesonide

Budesonide is a corticosteroid used to treat various inflammatory conditions like Crohn’s disease. When used regularly in its inhaled form, it can reduce the frequency and severity of asthma attacks, although it cannot stop an asthma attack that has already begun.

Two randomized controlled clinical trials in the U.K. examined whether people with COVID-19 benefited from using inhaled budesonide. However, it should be noted that neither trial studied hospitalized COVID-19 patients or those with severe disease, meaning that they can’t tell us how well budesonide works in those who are more seriously ill.

Published in July 2021, the STOIC trial looked at whether early use of inhaled budesonide—meaning within seven days of symptom onset—improved outcomes in the general population, such as the need for urgent care and self-reported symptom improvement^[1]. It included just under 150 people, half of whom received standard care while the other half received inhaled budesonide.

The researchers reported that early use of inhaled budesonide was associated with a lower likelihood of requiring urgent medical care and a shorter self-reported recovery time. That said, the trial stopped early in part due to national pandemic measures.

A larger trial (PRINCIPLE), published in August 2021, also looked at whether inhaled budesonide improved COVID-19 outcomes^[2]. It included 4,700 people: mainly those aged 65 years old and above, who were at a higher risk of COVID-19 complications. 1,073 people were randomized to the budesonide treatment group.

The researchers reported that the group treated with inhaled budesonide recovered sooner. However, on the whole, they didn’t find a meaningful difference in terms of patient survival or in the need for hospital admission in the group that received inhaled budesonide.

In December 2021, the National Institute for Health and Care Excellence (NICE) in the U.K., which provides national guidance for health and social care, removed inhaled budesonide from its list of recommended COVID-19 treatments.

The rationale for this decision was that both the STOIC and PRINCIPLE trials were conducted mainly in older people, meaning that the data wasn’t generalizable to other groups. Instead, NICE advised that inhaled budesonide be used only as part of ongoing clinical trials assessing its effectiveness.

In summary, while there is some evidence that inhaled budesonide may shorten recovery time in those with mild COVID-19, there’s not enough evidence indicating that it’s effective in all groups of people or that it reduces the risk of severe COVID-19 or COVID-19 mortality. That said, the scientific consensus does acknowledge other existing, cost-effective corticosteroids like dexamethasone as effective COVID-19 treatments for seriously ill COVID-19 patients.

Aspirin

Aspirin is commonly used to relieve pain and reduce fever. It’s also known for its blood-thinning effects, and there’s evidence that people with cardiovascular disease benefit from taking small, regular doses of aspirin to reduce the risk of blood clots.

Since COVID-19 is also associated with an increased risk of blood clots, researchers explored using aspirin to reduce the risk of blood clotting problems in COVID-19 patients who are hospitalized.

A U.S. study published in April 2021 looked at data from more than 400 patients during the early days of the pandemic (March to July 2020). It found that aspirin use was associated with a lower risk of invasive ventilation, ICU admission, and mortality in hospitalized COVID-19 patients^[3].

However, the authors cautioned that these findings were preliminary and insufficient for establishing a causal relationship. They called for randomized controlled trials to further investigate aspirin’s potential benefits.

One randomized clinical trial in the U.S., which included more than 650 outpatients, didn’t find meaningful differences between the aspirin-treated group and the placebo group in terms of reducing mortality or cardiovascular and pulmonary risk^[4].

Another trial (RECOVERY) led by researchers in the U.K. included 177 hospitals in the U.K., two hospitals in Indonesia, and two in Nepal. More than 14,000 patients were enrolled in the trial. The researchers reported that aspirin wasn’t associated with reduced mortality or risk of invasive mechanical ventilation^[5].

An epidemiological study in France, which examined the medical records of 31.1 million people, didn’t find that regular low-dose aspirin use was associated with a reduced risk of severe COVID-19^[6].

The COVID Treatment Guidelines website, operated by the U.S. National Institutes of Health, recommends against aspirin for people with mild COVID-19.

In summary, the scientific evidence available so far doesn’t demonstrate that aspirin offers clear benefits to COVID-19 patients.

Clarithromycin

Clarithromycin is an antibiotic used to treat bacterial infections. The COVID Treatment Guidelines website states that antibiotics shouldn’t be given “unless additional evidence for bacterial pneumonia is present”. In other words, while antibiotics could be used for people who have both COVID-19 and a bacterial infection, antibiotics aren’t COVID-19 treatments in themselves.

Similarly, NICE guidance states “Do not use antibiotics for preventing or treating COVID-19 unless there is clinical suspicion of additional bacterial co-infection”. It also warned of the risk of antimicrobial resistance as a result of unnecessary antibiotic use.

Broadly speaking, antibiotics aren’t used to treat viral infections as they are generally ineffective against viruses and such misuse can exacerbate problems with antimicrobial resistance. However, researchers are also aware that certain antibiotics could have antiviral and anti-inflammatory effects that could be useful for treating COVID-19.

A Cochrane review published in October 2021 examined 11 studies on the use of antibiotics for COVID-19 treatment. Evidence about clarithromycin’s effectiveness is scant, as all of these studies looked at azithromycin^[7], although it’s worth noting that azithromycin belongs to the same family of antibiotics as clarithromycin.

The authors of the review concluded:

“We are certain that risk of death in hospitalised COVID‐19 patients is not reduced by treatment with azithromycin after 28 days. Further, based on moderate‐certainty evidence, patients in the inpatient setting with moderate and severe disease probably do not benefit from azithromycin used as potential antiviral and anti‐inflammatory treatment for COVID‐19 regarding clinical worsening or improvement. For the outpatient setting, there is currently low‐certainty evidence that azithromycin may have no beneficial effect for COVID‐19 individuals. There is no evidence from RCTs [randomized controlled trials] available for other antibiotics as antiviral and anti‐inflammatory treatment of COVID‐19.”

Based on these results, they stated that “antibiotics should not be used for treatment of COVID‐19 outside well‐designed RCTs”.

We were unable to find mentions of clarithromycin specifically in the COVID Treatment Guidelines or the NICE guidance, suggesting that there isn’t sufficient scientific evidence to consider clarithromycin a COVID-19 treatment.

Why randomized controlled trials are more useful than anecdotes

Anecdotes or personal experiences can be a basis for formulating and studying a scientific question. In Bartlett’s case, his anecdotal experiences treating COVID-19 patients could have served as a basis for clinical trials to test the effectiveness of budesonide, clarithromycin, and aspirin combined.

However, anecdotes alone don’t provide quality evidence of a treatment’s effectiveness. One reason is because anecdotes are highly prone to bias. For instance, confirmation bias can lead a person to recall information that supports their preconceived beliefs—like a drug’s effectiveness—while neglecting instances where the drug doesn’t work.

Another potential pitfall is the lack of a proper experimental control. Without a control group, we can’t determine if any effects seen in the treatment group are due to the treatment itself or other variables unrelated to the treatment. Furthermore, both the control and treatment groups should be similar to each other, for example in terms of demographic factors like age and sex, as well as disease risk factors. This reduces the risk of these differences influencing the results.

Randomized controlled trials are considered the gold standard for evaluating a drug’s safety and effectiveness. When these trials are well-designed and well-performed, they mitigate important sources of bias, like those mentioned above.

For example, randomization ensures that the control and treatment groups are similar to each other. Data is also systematically collected and analyzed in a randomized controlled trial, reducing the effects of confirmation bias.

Conclusion

Overall, there isn’t reliable evidence indicating that budesonide, clarithromycin, and aspirin are effective treatments for COVID-19. Apart from anecdotes, Bartlett offered no new evidence to substantiate his claim that a combination of budesonide, clarithromycin, and aspirin is a “silver bullet” for COVID-19.

Randomized controlled trials are considered the gold standard when it comes to testing the safety and effectiveness of a medical treatment. Unlike anecdotes, randomized controlled trials contain several safeguards, such as experimental controls, blinding, and randomization, which help to reduce the risk of bias and improve the reliability of a trial’s findings.

REFERENCES

• 1 – Ramakrishnan et al. (2021) Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial. The Lancet Respiratory Medicine.
• 2 – Yu et al. (2021) Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. The Lancet.
• 3 – Chow et al. (2021) Aspirin Use Is Associated With Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019. Anesthesia and Analgesia.
• 4 – Connors et al. (2021) Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19: The ACTIV-4B Randomized Clinical Trial. JAMA.
• 5 – RECOVERY Collaborative Group. (2022) Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. The Lancet.
• 6 – Botton et al. (2022) No association of low‐dose aspirin with severe COVID‐19 in France: A cohort of 31.1 million people without cardiovascular disease. Research and Practice in Thrombosis and Hemostasis.
• 7 – Popp et al. (2021) Antibiotics for the treatment of COVID‐19. Cochrane Database of Systematic Reviews.