Testing New Treatments For Severe H1N1 Infection

Main Category: Swine Flu
Also Included In: Clinical Trials / Drug Trials;  Statins;  Endocrinology
Article Date: 12 Nov 2009 - 3:00 PST

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Quick 'bench-to-bedside' clinical trial would enroll 1,400 influenza patients to test corticosteroids and statins as potential treatments

An important, ground-breaking initiative is unfolding in the global critical care community in response to the H1N1 pandemic.

While front-line health care workers and infectious disease experts around the world are working round the clock to control, treat and prevent H1N1 infection, those who deal with the most severely ill patients - physicians working in hospital intensive care units (ICUs) - have joined forces to develop a more coordinated, long-term approach to H1N1.

In a commentary published in the medical journal the Lancet, St. Michael's Hospital's Dr. John Marshall describes this unprecedented initiative, which is called the International Forum for Acute Care Trialists (InFACT) H1N1 Collaboration. While the coalition against H1N1 is led by Canadians, dozens of groups whose members are involved in the care of critically ill influenza patients from every continent on the planet have already signed on.

"A core element of our initiative is to undertake clinical trials of simple, readily available and biologically plausible interventions that can be used to treat patients with severe H1N1 infection," says Dr. Marshall, a senior scientist in the Li Ka Shing Knowledge Institute at St. Michael's Hospital in Toronto who chairs the InFACT collaboration.

Will the clinical trials and the other initiatives planned by InFACT - such as a global registry of influenza victims and a "biobank" of blood samples - benefit people who are already sick or will fall ill over the next few months?

"Probably not," Dr. Marshall says. "But H1N1 isn't going away any time soon. We need to take a coordinated, evidence-based approach to understanding the natural history of the disease, to cataloguing current resources and gaps, and to looking for new and better treatments which may prevent or shorten hospitalization among those most seriously affected."

Proposed clinical trials to test new treatments

Canadian researchers are organizing several clinical trials aimed at finding new and more effective treatments for H1N1 infection.

One of these trials - the Collaborative H1N1 Adjuvant Treatment (CHAT) trial - seeks to enroll 1,400 patients, most of them Canadians, who are being treated in a hospital ICU for severe H1N1 infection and are on a ventilator. The mortality rate for these patients currently ranges from 10% over the first month. On average, those who survive spend two weeks in the ICU.

Right now H1N1 infection is treated with anti-viral drugs and other supportive measures. But researchers want to evaluate two classes of common, readily available drugs which have shown promise in limiting the severity of H1N1 infection.

"Anecdotal reports and data from animal studies suggest that corticosteroids and statins may dampen the inflammatory response that leads to severe illness and death from H1N1," says Dr. Marshall. "None of these drugs has been adequately studied for efficacy."

Even though no specific data show them to be effective, right now more than half of patients with severe H1N1 infection are treated with corticosteroids - hormones given to reduce swelling and decrease the body's immune response. This is based largely on the observation that corticosteroid drugs have proven useful in treating severe acute lung injury.

A recent study of patients with seasonal influenza found that those who were taking statins when they got sick had a better prognosis than those were not. These drugs are currently taken by millions of people take to help control cholesterol levels and prevent heart disease.

This accelerated "bench-to-bedside" approach is key to success against pandemic influenza and other infectious diseases, says Dr. Marshall. "Research during a pandemic poses unique ethical and logistical challenges. It usually takes years to mount a major clinical trial. But in the case of H1N1 our goal is to drastically shorten this to a period of weeks or a few months without compromising scientific and ethical integrity," he explains.

While funding is needed for the clinical trials to proceed, that time is too short to achieve this through conventional means. "Instead, we've adopted an incremental funding strategy. This means we're seeking money that will allow us to launch the trials and moving ahead with confidence that additional funds can be found," he says.

About the InFACT H1N1 Collaboration

The Canadian-led International Forum for Acute Care Trialists (InFACT) H1N1 Collaboration is a unique and unprecedented attempt to gain control over a new pandemic illness (go to http://www.infactglobal.org).

According to Dr. John Marshall who chairs the group, it is currently organized around three core initiatives:

• A common global registry listing all patients critically ill due to H1N1 infection. The registry, which has been created out of five existing databases around the world, will enable real-time study of the epidemiology, clinical course, and treatment of severe H1N1 disease. In parallel, the group hopes to develop a "biobank" - a repository of samples of blood and other material taken from people infected with H1N1 - which will allow for studies of genetic susceptibility and clinical biology. The registry will also help scientists understand how H1N1 infection varies around the world in response to local medical capacity and treatment approaches.
  
  
• A program of accelerated randomized clinical trials aimed at quickly identifying, testing and delivering new treatments. The first group of clinical studies will evaluate inexpensive interventions that are available in both the developed and the developing world. The research will use so-called "adaptive designs" which ensures that positive results can be quickly incorporated into practice and that ineffective treatments are quickly dropped.
  
  
• The first-ever catalogue of critical care capacity around the world. Any coordinated and effective plan for dealing with H1N1 or another severe pandemic illness requires a host of resources - hospital ICU beds and ventilators, a steady supply of vaccines and medications, and enough health care providers to use them. The group hopes to catalogue international critical care capacity, and also to promote, mentor, and support clinical research activities in resource-poor areas where the human toll is likely to be the greatest.

About the H1N1 Pandemic

The new influenza strain is already a problem that is being felt by professionals across the health care spectrum - from those working to develop and deliver an effective vaccine to those treating the severest cases of H1N1 infection in hospital ICUs.

By early October, 2009, there had been more than 340,000 reported cases of H1N1 infection in 191 countries and more than 4,100 deaths. The World Health Organization initially projected that up to two billion people could become infected over a two-year period. While vaccination programs and other factors should reduce this number, it's estimated that between 200,000 to 10 million people infected by H1N1 might be sick enough to require intensive care in hospital.

Source: Julie Saccone
St. Michael's Hospital