Prof Alistair Nichol is involved in trials on Covid patients, using wisdom from previous epidemics, writes Seán Duke
When the Covid-19 pandemic hit, Professor Alistair Nichol was a little more prepared than most.
The intensive care consultant, currently at St Vincent’s University Hospital (SVUH), was a doctor based in Australia back in 2009 when swine flu hit.
During that outbreak, it proved logistically impossible for hospitals globally to rapidly test new and potentially life-saving treatments on patients in ICU.
Lessons were learned, however, and now additional ‘real time’ trials for Irish Covid-19 patients in ICU have begun at SVUH.
These trials are the latest addition to a trial (REMAP-CAP) that has found three effective treatments for Covid-19 already.
The fact that these new trials are happening – the latest ones testing the effectiveness of anti-coagulant drugs and the other investigating the use of ACE inhibitors – is due to the pre-planning of doctors, like Prof Nichol.
Belfast man Prof Nichol is Director of the Health Research Board-funded, Irish Critical Care Clinical Trials Network at University College Dublin.
He and his colleagues had been frustrated in their efforts in 2009 to set up trials while the swine flu pandemic raged.
Over the next few years, Prof Nichol and colleagues in Ireland and overseas worked hard to build up the infrastructure to ensure that life-saving clinical trials could begin immediately when the next pandemic hit.
In March 2020, when Covid landed, the preparatory work began to pay off.
When I spoke to him in 2015 he said: “For the first time in human history, doctors and researchers in ICU can get ahead of a pandemic and be ready for it.”
“During the swine flu pandemic a lot of money and effort was put into strategies which may, or may not work,” Prof Nichol said, citing the €2.17bn spent by various governments on Tamiflu in 2009 despite its unknown effectiveness against swine flu.
To this day, this question remains unanswered.
Prof Nichol recalls how there was not enough time to capture initial information from patients coming into Australia hospitals with H1N1.
“This required medical protocols to be set up, ethical approvals given and specialist nurses to be put in place, but by the time this was all completed, the virus had passed through and the chance was missed.”
The way clinical trials involving people in ICU work is that people give consent directly, if they are capable, or indirectly through the assent of their family members if they are unable to actively engage in these conversations.
Afterwards, for those that recover, they are then asked whether they would like to continue with the trials.
The availability of clinical trials gives people with Covid in ICU in Ireland the ability to safely access new, potentially life-saving treatments that might not otherwise be available here.
They provide doctors with the means to quickly answer questions about the effectiveness of using particular drugs, for example, steroids against Covid-19 (they work), or hydroxychloroquine (it doesn’t and might even be harmful).
The numbers dying in any pandemic, even the less deadly ones, are enormous.
The H1N1 virus that caused swine flu is estimated to have caused 284,000 deaths globally, according to a WHO study.
However, despite this level of mortality, Prof Nichol believed that if researchers worked together globally, it could be “much better the next time”.
Another reason the world dodged a bullet in 2009 was that swine flu was not the flu epidemic specialists were expecting, and not remotely as deadly as the Spanish flu which killed between 50 and 100 million people globally between 1918 and 1920. The swine flu deaths ended up roughly similar to seasonal flu, which kills 300,000-650,000 every year.
The bad news is that despite Covid, the world is still due another big flu pandemic. “There is no reason why another flu pandemic couldn’t happen at any time, even while Covid is around,” says Prof Nichol. “The clock is still ticking on that one.”
The good news is that in Ireland, thanks to the foresight of Prof Nichol and many medical colleagues, the protocols, paperwork, and permissions were in place for clinical trials to begin immediately when a major flu pandemic arrived. When Covid landed instead, they were ready to pivot accordingly.
The Covid clinical trials starting at SVUH will be rolled out to other Irish hospitals.
Covid patients will get the chance to benefit from new treatments, some of which might otherwise not be available in this jurisdiction. The trials are also part of a global trial network, that Prof Nichol’s work helped establish, including Australia and New Zealand, where different waves of infections occur at different times.
After H1N1 had come and gone, hospitals around the world were none the wiser about what treatments did and didn’t work against H1N1.
“We lived, but we didn’t learn,” said Prof Nichol. He wondered how things could be done better next time and continued to do so after he took a post at SVUH.
He linked with colleagues at the University of Oxford based International Severe Acute Respiratory Consortium (ISARIC) and the Australian and New Zealand Intensive Care Research Centre (ANZICRC). They began to put everything in place so that hospitals in both the northern and southern hemisphere involved in the trial would be able to collaborate and be fully prepared for the next big flu pandemic.
The European Commission provided €26m in funding support for the European-based part of a proposed project (PREPARE), which would include a hospital in Ireland, as well as €4m for Australian partners and €1m for medical researchers based in New Zealand.
The funding was to support a clinical trial investigating pneumonia in the ICU, but much else besides.
The trial would capture information from patients with pneumonia coming into the ICU in terms of what the response was to ventilation, to antibiotics and whether steroids were required.
However, the unique point of this study was that if a pandemic struck, the trial was flexible enough in design to be able to quickly shift to focusing on getting information about the new virus.
In March 2020 when Covid struck, everything was in place for clinical trials to start immediately, and for answers to be found.
The trials quickly found that steroids do work for treatment of Covid-19 patients in ICU, while the hydroxychloroquine, championed by former President Donald Trump, did not.
Later in 2020, trials at SVUH and other centres looked at the effectiveness of anti-coagulant drugs such as Heparin on people in ICU with Covid.
It was found that these drugs produced better medical outcomes for people with Covid on the regular hospital wards, but worse results for those in the ICU.
This finding, which was published in the New England of Journal of Medicine, naturally led on to a follow-up trial, beginning at SVUH last week.
It seeks to determine whether people in ICU with Covid do better when they are given a reduced dose of anti-coagulant drugs, or not given anti-coagulants at all.
“We have answered more questions about what works and doesn’t work in viral pneumonia (Covid and flu) over the last 18 months, than we answered in the previous 10 years,” says Prof Nichol. “These trials give us the opportunity to respond in the middle of a pandemic and improve medical outcomes for our ICU patients.
“Clinical trials give us the answers we need. They save time and money for the health service, but, most importantly, they can save lives.
“It is important that we take part in these trials in Ireland, so that we know the answers are relevant to an Irish setting, and to improve standards of care.
“Covid has been scary, but it is not the big flu pandemic like the Spanish flu that we know will eventually come,” he adds.
“These are not once-off events, as there is a pandemic, on average, every 23 years. The clinical trials know-how we have gained during Covid, will, however, help us when the next one hits.”