10 years after sepsis break-through: We’re building a test machine

Milestone clinical trial at Rigshospitalet has gone around the world. New figures show that the trial has saved DKK 52 million, 4,400 unnecessary blood transfusions and 1,184 lives - and that’s in Denmark alone.

Professor Anders Perner is the main architect behind one of the most exciting studies in Denmark in recent times. His research into fluid treatment for intensive-care patients with blood poisoning has gone around the world and has changed clinical practice globally: with repercussions and protests from industry as a result. Today, 10 years after he began his first trials, Anders Perner looks back, but also very much forward, because his mission is far from accomplished.

“We’re going to build a ‘test machine’ to ensure that, every time we introduce a new treatment, we have a platform to systematically test the treatment for the first year after introduction: whether it works, whether it’s necessary, or whether it actually does more harm than good,” said Anders Perner. 

More clinical research: Summersault for health

Even though the group of researchers under Anders Perner’s leadership have long since justified their existence, among other things with their ground-breaking 6S trials, clinical research is often like banging your head against a brick wall, because there are no resources or commercial interests in launching clinical trials to test treatments close to patients. 

“For many years, we’ve been in the habit of doing something that we actually haven’t got particularly good evidence will work - fluid treatment for patients with blood poisoning. We’re in a situation where drugs companies don’t have much interest in the area, because it’s difficult to make money producing saline solution. Therefore, there’s not much research on the effect. This type of research requires public funding instead, foundation grants and philanthropic donations, and now we’ve got this to carry out a major new trial to examine whether what we’ve been doing for a long time now is actually the right thing to do,” said Professor Anders Perner, who is Head of Research for CRIC (Centre for Research in Intensive Care) and a consultant at the Department of Intensive Care at Rigshospitalet.

Anders Perner’s great wish is that more of us realise the importance of investing in close-to-patient research. And his wish is no castle in the sky. All the six clinical trials completed by the research group to date have shown that treatment was unnecessary, or directly harmful. This demonstrates that more clinical trials would make sure that we don’t make the same mistakes again and again. We need a new platform for all these trials, says Anders Perner.

“My proposal is that we turn everything upside-down in a structural summersault and rethink the way in which we organise our health service with regard to introducing new treatments. We have to strengthen the health-service platform for clinical trials of what we’re introducing. More specifically, political and regional decision makers have to allocate more resources and funds to much more close-to-patient research. We have to prioritise research that can contribute to health with clinical conclusions on what treatments benefit most patients,” says Anders Perner, and he continues:

“It’s something of a paradox that today, 10 years after our break-through with the 6S trial, we can conclude that, even though it clearly makes sense to invest in clinical research, it has only become more difficult and more administratively burdensome to carry out these trials, even though studies have shown that a quarter of everything we do in the healthcare sector actually has no benefit for patients.

Overuse of antibiotics is the climate crisis of the health services

Antibiotics use is one of the areas that Anders Perner and his colleagues want to take a serious look at, with clinical research in international collaboration with other intensive care departments.

“WHO has estimated that overuse of antibiotics will result in an increase in annual deaths from blood poisoning from 5 million to 15 million in 2050. This is the climate crisis of the health services, and we really must take it a lot more seriously. One of the instruments in efforts should be clinical trials, and better evidence from these for how much antibiotic is really necessary for patient treatment. However, the path is littered with administrative and legislative obstacles, as well as lack of investment. I hope that we can change this by finding the structural and economic conditions we need to carry out clinical trials. This will save lives, and it will save us from the looming antibiotics crisis,” concludes Anders Perner.

Blood poisoning and fluid treatment

Blood poisoning (sepsis) is a strong inflammatory reaction that it is released when an infection spreads to the blood, and it may lead to failure of the circulatory system. The primary infection is often pneumonia or a urinary tract, intestinal or skin infection. Bacteria can also enter the blood through a central IV drip that many patients have for chemotherapy or long-term antibiotics treatment. The first life-saving treatment for blood poisoning is to stabilise the circulation. You can do this by means of two different fluids: starch or saltwater. After the results of the 6S trial, Denmark and many other parts of the world have stopped using starch as a fluid treatment.

About the 6S sepsis trial

The trial included 798 patients with severe blood poisoning who were admitted to intensive care departments in the Nordic countries. Half of the patients received standard treatment with hydroxyethyl starch (HES). The other half were treated with Ringer’s acetate saline solution.

Of the 398 patients who received fluid treatment with HES, 201, or 51 per cent, died in the course of 90 days. Many needed dialysis and blood transfusions. Of the 400 patients who received fluid treatment with saline solution, 172, or 43 per cent, died in the course of 90 days. 

The 6S study was launched on 23 December 2009 and the results were published in the New England Journal of Medicine in June 2012. The trial was financed by the Danish Council for Strategic Research.

Link to the article in the New England Journal of Medicine

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