Critically ill patients with COVID-19 who are given a drug that reduces inflammation by modifying the immune system require less time receiving intensive care treatment, an international study has found.
The early findings, which are yet to be published, come from the REMAP-CAP clinical trial. New Zealand’s participation in the trial is coordinated by the Medical Research Institute of New Zealand and funded by the Health Research Council and Ministry of Health.
The findings show that treatment with the immune modulator ‘tocilizumab’ reduced time spent on organ support* in intensive care among critically ill patients with severe COVID-19, compared to patients who did not receive any immune modulation treatment.
Due to the clinical implications for patients, the researchers have released the findings before they have been peer-reviewed, but are working to analyse and publish the full results as soon as possible.
Dr Colin McArthur, intensivist and researcher at Auckland City Hospital who leads the New Zealand arm of the trial, says these early findings indicate that tocilizumab is effective for critically ill COVID-19 patients in intensive care units. “Once we’ve completed the analysis of the full dataset, we will know if these findings can help critical care teams around the world to improve the outcomes of severely ill COVID-19 patients.”
The latest analysis was carried out by a statistical analysis committee separate from the trial investigators and reviewed by an independent Data and Safety Monitoring Board (DSMB) on 17th November. The analysis included data from the first 303 patients randomised to receive immune modulation treatments: tocilizumab, sarilumab, anakinra, interferon, or no immune modulator.
Patients receiving tocilizumab were more likely to improve (measured by a combination of organ support requirements in the ICU and hospital survival) compared to patients who received no immune modulator. However, the trial has not yet determined the relative benefits of tocilizumab compared to the other immune modulators. Further data is expected in the coming weeks and months.
The trial data yielded an estimated odds ratio of 1.87 for a better outcome with tocilizumab compared to no immune modulation, with a high degree of statistical certainty (99.75% probability that tocilizumab is superior to no immune modulation).
In addition to these findings, the latest analysis also revealed the antiviral drug Kaletra (lopinavir/ritonavir) to be ineffective and provide no additional benefit to critically ill COVID-19 patients, compared to those who did not receive the drug.
REMAP-CAP began investigating treatments for COVID-19 in March 2020, enrolling hospitalised patients with either moderate or severe (requiring ICU care) COVID-19 disease.
The study design randomises patients to multiple combinations of treatments, enabling researchers to evaluate different treatments for COVID-19, including antivirals, drugs which modulate the immune response, and therapies that modulate or support other vital aspects of the body's response to the virus.
In total, over 2,000 patients in 15 countries have been enrolled at more than 260 hospitals worldwide. The effects of interventions are assessed separately for moderate and severely ill patients.
The latest findings on tocilizumab and lopinavir/ritonavir add to REMAP-CAP findings from earlier this year, which found that hydrocortisone steroid treatment improved recovery among critically ill COVID-19 patients.
“This is an absolutely amazing result,” says Dr Lennie Derde, Chair of the study’s immune modulation domain working group and consultant in intensive care medicine at the University Medical Centre in Utrecht, the sponsor of the study in Europe. “To have a second effective therapy for critically ill patients within months of the start of the pandemic is unprecedented. Specific targeting of the immune response is theoretically attractive, and now we have shown it works.”
*Refers to treatments to support breathing (mechanical ventilation or non-invasive ventilation) or circulation (vasopressors).
REMAP-CAP (The Randomised Embedded Multifactorial Adaptive Platform for Community Acquired Pneumonia) is an ongoing adaptive clinical trial involving more than 2000 COVID-19 patients at more than 260 clinical sites around the world, including 11 within New Zealand.
REMAP-CAP continues to evaluate multiple other treatments, including therapeutic anticoagulation, antiplatelet agents, apremilast, eritoran, anakinra, sarilumab, vitamin C, simvastatin, convalescent plasma, macrolides, and antibiotics.