Clinical trial with ICU patients with COVID-19 shows 99% effectiveness

20th November 2020

Tocilizumab effective in treating sickest COVID-19 patients

– Clinical trial with ICU patients with COVID-19 in St. Vincent’s University Hospital shows 99% effectiveness
– Over 2,000 critically ill patients globally now enrolled in trial across 260 hospitals

Critically ill patients with COVID-19 treated with a drug that reduces inflammation by modifying the immune system are less likely to die and spend less time in intensive care, an international study has found.

The early findings, which are yet to be published, come from the REMAP-CAP trial, led in Ireland by St. Vincent’s University Hospital and University College Dublin and globally by Imperial College London, Intensive Care National Audit & Research Centre (ICNARC) in the UK, and Utrecht University in Europe.

The findings, involving 260 hospitals worldwide, has shown that treatment with the immune modulator tocilizumab was 99 per cent more likely to reduce deaths and time spent in intensive care among critically ill patients with severe COVID-19, compared to patients who did not receive the treatment.

Professor Alistair Nichol, Consultant in Intensive Care Medicine at St. Vincent’s University Hospital Dublin and Chair in Critical Care Medicine at University College Dublin said: “These early findings show that this immune modulating drug can significantly improve the outcomes for the most severely ill COVID-19 patients in intensive care. Once we have completed the analysis of the full dataset, we hope these findings will allow critical care teams around the world to improve the outcomes of the sickest COVID-19 patients.”

In addition, the latest analysis also revealed an antiviral drug 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.

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.

The latest analysis was carried out by the Data and Safety Monitoring Board (DSMB) on 17^th November and reviewed data from the first 303 patients randomized to receive immune modulation treatments: tocilizumab, sarilumab, anakinra, interferon, or no immune modulator.

Patients receiving tocilizumab were 99 per cent more likely to improve (measured as survival or a shorter period of organ support in ICU) compared to patients who received no immune modulator. However, the trial does not yet know the relative benefits of tocilizumab compared to the other immune modulators. Further data are expected in the coming weeks and months.

The DSMB reported an estimated odds-ratio of 1.87 for a better outcome with tocilizumab compared to no immune modulation, with a 99.75% probability that tocilizumab is superior.

Secondly, analysis of treatment with lopinavir/ritonavir was found to be ineffective, with an estimated odds-ratio of 0.67 (worse than control) with a 99.9 per cent probability of futility (an effect less than 1.20).

REMAP-CAP began investigating treatments for COVID-19 in March 2020, enrolling hospitalized patients with either moderate or severe (requiring ICU care) COVID-19 disease.

The study design randomizes 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.

Over 2,000 patients have been enrolled now, including more comparing the different immune modulating drugs, at more than 260 hospitals worldwide and randomized to multiple treatment combinations. 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”, said Doctor Lennie Derde, Consultant in Intensive Care Medicine at the University Medical Center in Utrecht, the sponsor of the study in Europe, and the Domain Specific Working Group Chair. “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”.

The study is funded in Ireland by the Health Research Board as part of the Irish Critical Care-Clinical Trials Network (ICC-CTN)  which was established in 2015 to support research being conducted by the Irish Critical Care – Clinical Trials Group (ICC-CTG) – located within the Clinical Research Centre (UCD-CRC) at St. Vincent’s University Hospital. In addition, University Hospital Galway, The Beacon Hospital and Beaumont hospital are also participating in the trial will more Irish hospitals to join shortly.

REMAP-CAP

REMAP-CAP (The Randomized 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.

REMAP-CAP continues to evaluate multiple other study questions, including therapeutic anticoagulation, antiplatelets, apremilast, eritoran, anakinra, sarilumab, vitamin C, simvastatin, convalescent plasma, macrolides, and antibiotics.