New Study from ANZIC Researchers Casts Doubt on Ivermectin for Hospitalized COVID-19 Patients

A groundbreaking randomized clinical trial conducted by the Australian and New Zealand Intensive Care Research Centre (ANZIC) has delivered compelling evidence that ivermectin, the antiparasitic medication once hailed as a potential COVID-19 treatment, does not significantly improve outcomes for hospitalized patients in New Zealand and Australia. The IVECT trial, published in the prestigious journal Critical Care Medicine, examined both critically ill and noncritically ill individuals, providing clarity amid years of conflicting data on the drug's efficacy during the pandemic.

This research, involving sites across New Zealand including Auckland City Hospital and Middlemore Hospital, underscores the rigorous scientific approach taken by Kiwi academics and clinicians. As New Zealand continues to refine its post-pandemic healthcare strategies, findings like these highlight the vital role of local universities in advancing evidence-based medicine.

The Controversial History of Ivermectin in COVID-19 Treatment

Ivermectin, discovered in the 1970s and widely used for parasitic infections like river blindness, gained notoriety during the COVID-19 pandemic. Early in vitro studies suggested it could inhibit SARS-CoV-2 replication at high concentrations, sparking global interest. Proponents, including some public figures, promoted it as a cheap, accessible 'miracle drug,' leading to widespread off-label use despite limited high-quality evidence.

In New Zealand, where COVID-19 waves were managed effectively through vaccination and public health measures, ivermectin use remained limited due to regulatory caution from Medsafe. However, international hype influenced some patients and clinicians, prompting calls for local trials. The IVECT study emerged from this context, embedded in the larger platform trial framework to efficiently test multiple therapies.

Previous meta-analyses showed mixed results: some small trials reported benefits in mortality or recovery time, while larger RCTs like those from Brazil and the UK found no effect. The controversy peaked with retracted studies and debates over data integrity, emphasizing the need for robust, multicenter trials like IVECT.

Design and Methodology of the IVECT Trial

The IVECT (Ivermectin in COVID-19) trial was a multinational, double-blind, placebo-controlled randomized clinical trial conducted across 28 sites in Australia and New Zealand. It recruited 153 hospitalized patients with confirmed COVID-19 between 2021 and 2023, during the Delta and Omicron waves.

• Critically ill group: 62 patients requiring organ support, such as mechanical ventilation or vasopressors.
• Noncritically ill group: 91 patients not needing advanced support but hospitalized due to moderate symptoms.

Participants received either ivermectin at 400 μg/kg daily for up to 5 days or matching placebo, alongside standard care. The primary outcome was organ support-free days at day 28, a composite measure capturing survival without respiratory or cardiovascular support. Secondary outcomes included hospital mortality, ventilator-free days, and adverse events.

Ethical approvals were obtained from institutional review boards, including those at the University of Auckland and Monash University, ensuring participant safety. Statistical analysis used Bayesian methods for efficiency in this adaptive platform design.

Key Findings: No Significant Benefit Observed

The trial's results were unequivocal. In critically ill patients, hospital survival was 80.6% with ivermectin versus 75.0% with placebo, a non-significant difference. For noncritically ill patients, survival rates were nearly identical at 95.7% versus 96.8%. The primary outcome showed no improvement in organ support-free days.

Secondary endpoints, including duration of ventilation and ICU stay, also favored neither arm. Adverse events were similar between groups, with no excess toxicity from ivermectin. These findings align with global consensus from WHO and FDA, which do not recommend ivermectin outside trials.

In New Zealand's context, where COVID-19 mortality was low (around 3,000 deaths total), this study reinforces that standard therapies like dexamethasone and antivirals remain superior.Read the full study abstract on PubMed.

New Zealand's Contribution: Universities and Hospitals Lead the Way

New Zealand institutions played a pivotal role. The University of Auckland, through its faculty in the ANZIC Centre, coordinated recruitment at Auckland City Hospital and Middlemore Hospital. Researchers like those from the Medical Research Institute of New Zealand in Wellington contributed expertise in trial design and data analysis.

This collaboration exemplifies how Kiwi higher education drives international research. Universities like Auckland and Otago have long histories in critical care, with ongoing programs in infectious diseases. The study highlights opportunities for postdocs and lecturers in clinical trials, bolstering NZ's reputation in global health research.

Comparing IVECT to Global Ivermectin Trials

IVECT adds to a body of over 100 trials. Early positive signals from small studies (e.g., Iranian RCT showing 82% mortality reduction) contrasted with larger ones like TOGETHER (Brazil, no hospitalization benefit) and PRINCIPLE (UK, no recovery acceleration).

• Positive trials: Often small, unblinded, or low-quality.
• Negative trials: Larger, blinded RCTs like ACTIV-6 (US) and LODEINE (India).

Meta-analyses now converge on no benefit for hospitalized patients, shifting focus to early outpatient use—where evidence remains weak.

Clinical Implications for New Zealand Hospitals

For NZ clinicians, IVECT supports guidelines from the Ministry of Health and Te Whatu Ora, prioritizing remdesivir, Paxlovid, and steroids. It discourages ivermectin, reducing risks of self-medication and drug interactions.

During Omicron, NZ saw ~1 million cases with low hospitalization rates (thanks to vaccination), but critically ill patients strained ICUs. This study aids resource allocation, emphasizing proven therapies. Long-term, it informs preparedness for future pandemics.Access the IVECT trial publication.

Boosting Academic Careers in NZ Critical Care Research

The IVECT trial showcases career pathways at NZ universities. Researchers at the University of Auckland's School of Medicine gained publications in top journals, enhancing grant success and international collaborations. Similar opportunities exist in Otago's Division of Health Sciences and Canterbury's faculty.

For aspiring lecturers or postdocs, involvement in ANZIC trials builds expertise in adaptive designs and Bayesian statistics, key for funding from Health Research Council NZ.

Challenges and Lessons from Pandemic Research in NZ

Conducting trials during lockdowns required innovative recruitment and remote monitoring. Ethical dilemmas around placebo use in desperate times were navigated carefully. NZ's small population necessitated multinational efforts, fostering ANZIC's strength.

Funding from MBIE and philanthropic sources was crucial, highlighting needs for sustained investment in university research infrastructure.

Future Outlook: NZ Universities Pioneer Next-Gen Therapies

Post-IVECT, ANZIC focuses on long COVID and novel antivirals. University of Auckland leads mRNA research, while Wellington advances AI for ICU prediction. These efforts position NZ as a hub for Pacific health innovation.

Actionable insights: Clinicians should stick to guidelines; researchers pursue adaptive trials; policymakers fund higher ed research.

Stakeholder Perspectives on the Findings

NZ intensive care specialists praise IVECT's rigor, noting it ends uncertainty. Patient advocates appreciate clarity, avoiding false hope. Academics at UoA emphasize evidence-based practice training for med students.

Photo by Annie Spratt on Unsplash