CRICS-TRIGGERSEP (F-CRIN) takes stock of this little-known disease, of which there are an estimated 49 million cases and 11 million deaths per year worldwide.
Interview with Pr. Ferhat Meziani (Head of the Intensive Medicine-Resuscitation Department at the New Civil Hospital – CHRU Strasbourg) and Pr. Stephan Ehrmann (Intensive Medicine-Resuscitation – Tours University Hospital), coordinators of the CRICS-TRIGGERSEP network labeled F-CRIN .
Can you briefly describe the disease and its incidence?
Sepsis is the most serious form of an infection (bacterial, viral, fungal or parasitic) which causes organ failure with a life-threatening risk for patients. The disease mainly affects the lung – for example, a bad cough that sets in, degenerates, with late management, and becomes a general infection, but it can affect any other organ (kidneys, gallbladder …).
Every year, there are an estimated 49 million cases of sepsis worldwide, of which more than 40% of cases occur in children under 5 years old. The number of deaths linked to sepsis is estimated at 11 million per year worldwide. In France, hospital mortality is estimated at 25%, with a higher frequency in patients over 75 or with comorbidities ( cancer, heart failure, immune deficiencies, etc.), and in children under 1 year old. It is a disease that affects the most fragile in the broadest sense.
What are the current treatments for affected patients?
The main treatments for sepsis are antibiotics and resuscitation. Unfortunately, we have no specific treatment identified. The principle of emergency corticosteroid therapy has recently been developed – a symptomatic treatment of inflammation, to reduce the risk of an unfavorable evolution. Everything remains to be refined to know who will respond well to the treatment. Our network, under the leadership of Pr. Annane with the CRICS-TRIGGERSEP network, has set up a trial platform which allows patients to be included in therapeutic trials in a systematic and large-scale way, in order to identify patients most at risk. even respond to corticosteroids, in a personalized medicine approach. The challenge is knowing how to give the right treatments to the right patients.
What are the latest advances in clinical research of CRICS-TRIGGERSEP on sepsis. How are they innovative?
The latest advances in sepsis are the personalization of treatments, corticosteroid therapy, and the development of clinical trials that allow testing of several existing or new molecules to optimize trials.
Our research concepts in the network have evolved: we include patients as we go along, but we stop a study if we realize that the drug tested does not work – we speak of adaptive trials. Currently, the network is participating in several trials:
REMAP-CAP, led by an international consortium coordinated by the University of Utrecht, in the Netherlands, in which the network is involved: it is an adaptive trial which focuses on pulmonary sepsis of community origin to test several molecules associated with antibiotics. RECORDS, a national platform trial project led by Pr. Djillali Annane (AP-HP) within the network, which is interested in the personalization of treatment of patients with hydrocortisone and fludrocortisone, according to genetic predisposition. CAPE COD, led by Pr. Pierre-François Dequin (Tours University Hospital) who is interested in severe community-acquired pneumonia and corticosteroids to improve the vital prognosis of patients with sepsis in intensive care. ANTHARTIC, led by Dr. Bruno François (Limoges University Hospital), which is studying pulmonary sepsis following cardiac arrest and the provision of an early antibiotic to avoid lung infection and better prevent sepsis. AMIKINHAL, led by Pr. Stephan Ehrmann (Tours University Hospital), who is interested in treatments by an original route of administration represented by antibiotic therapy delivered directly into the lungs by inhalation in order to prevent nosocomial pulmonary infections.
What is the contribution of the networks in the management of the disease?
Networks like ours, by organizing and professionalizing clinical research, allow the inclusion of patients in trials 24/7. This is one of the peculiarities of this disease compared to others. Because during sepsis, you have to give a drug very quickly, ideally within 6 hours. It is a particular logistical and organizational challenge. Thanks to our organization, we are able to carry out emergency trials, we include more patients and research progresses more quickly.
What are the other advances in the care of patients and their families?
All the research goes towards a better knowledge of the patients for a personalization of the treatments in the short term but also beyond. Certain molecules clearly show a benefit in the evolution of patients. Sepsis, which until a few years ago was unknown, is becoming a priority for the World Health Organization and a national priority.
Overall, there is a decrease in the mortality of patients in intensive care with sepsis in the short term but also at D+90, an increase in patients who are discharged alive, better prevention of the occurrence of infections and therefore of sepsis and lesser sequelae etc. We saw this recently with COVID, there is now a whole field of research developing on the sequelae of patients who have survived sepsis: surviving sepsis, at what cost and for what quality of life in the medium term ? It is a field of research that is invested in to improve the long-term benefit of patients and their families.
In France, we have opened intensive care units to families. It’s a big step forward. These services are open 24 hours a day and this allows a closer relationship with the family, essential to obtain consent to participate in a study, when the patient is not in a condition to give it.
How can patients participate in current or future studies?
The inclusion of patients is done within the framework of national and European regulations; the inclusion of emergency patients in the context of resuscitation is a particular challenge. Some patients are not immediately able to give their consent, in the context of an emergency it is with the family and relatives that we exchange, consent is immediately obtained from the patient as soon as possible as for all clinical research . Anyone interested in our studies can come forward by contacting us via our website (https://www.crics-triggersep.org/).
Will 2022 be a strategic year for the disease?
Yes, the years 2022 and 2023 are strategic because we are witnessing an awareness in the field at the French level and we are starting to obtain large-scale public funding (PHRC, RHU). By the end of the year, early 2023, we should have the results of the AMIKINHAL and CAPE CODE studies. In addition, this year, Inserm is supporting the initiative of a group of experts, of which we are a part, bringing together clinicians, veterinarians and basic research laboratories who are thinking in an organized way about research on sepsis, to that it be more visible, inclusive and funded at significant levels.
What is the contribution of the F-CRIN network for the disease?
F-CRIN has labeled our network and provides us with all its support, funding (e.g. a project manager who allows the coordination of the various centres), assistance in communication, interaction with INSERM and the provision of aid units in setting up projects to obtain European funding. The network facilitates our administrative procedures and improves our visibility. This is a big plus for French research.
What are the next events on SEPSIS?
Apart from the world day which takes place on September 13, we are organising, within the framework of the Inserm expert committee, on September 8, 2022 at the Ministry of Health, a sepsis awareness day, dedicated to the sphere medical, veterinary and fundamental research.
Do you have any advice for the patients and families who read us?
As this disease is still little known and can degenerate rapidly, we recommend that patients contact their doctor as soon as an infection sets in over time and worsens. It is the attending physician who will assess the degree of infection and refer the patient urgently if he suspects sepsis.
A propos de CRICS-TRIGGERSEP : Clinical Research in Intensive Care and Sepsis – TRIal Group for Global Evaluation and Research in SEPsis
Labeled “network of excellence” by F-CRIN in 2013, CRICS-TRIGGERSEP is a European network made up of 28 hospitals in France and Belgium, specializing in research on the disease of sepsis which affects nearly 49 million people in the world each year and causes 11 million deaths per year. Its objective: to better understand and improve the management of this disease. It includes 5 working groups distributed in such a way as to optimize the skills of each of the professionals involved in this research, coordinated by Pr F. Meziani and Pr S. Ehrmann. The network has to its credit 89 industrial and academic clinical studies with in 2020, 4817 patient inclusions. CRICS-TRIGGERSEP also participates in quality scientific publications, among others, in The Lancet, JAMA and The New England Journal of Medicine with in 2021 a total of 66 publications related to COVID-19 and 32 publications on other subjects. .
More information : https://www.crics-triggersep.org/
A propos de F-CRIN : French Clinical Research Infrastructure Network
Created in 2012, supported by INSERM and funded by the ANR and the Ministry of Health, F-CRIN (French Clinical Research Infrastructure Network) is an organization of excellence serving French clinical research. It aims to strengthen competitiveness? of French clinical research has? internationally, to identify and label research networks, to facilitate the implementation of academic or industrial clinical trials, and to develop the expertise of clinical research players, by pooling know-how, objectives and means. The organization, which has a localized national coordination unit has? Toulouse, has already? label? and currently federates 16 clinical investigation networks targeting diseases of general international interest (Severe Asthma, Stroke, Cardiology, Cardi-ne?phrology, Atopic dermatitis, Autoimmune and auto-inflammatory diseases, Cardio- diseases, Cardiovascular diseases, Motor neurone disease/Charcot’s disease, Obesity?, Retinal pathologies, Parkinson’s and movement diseases, Pediatrics, Multiple sclerosis, Sepsis Thrombosis, Psychotic disorders, Vaccinology), 3 networks of expertise and methodology (Rare Diseases, Medical Devices, Epidemiology) and a tailor-made support platform offering all the services necessary for? the conduct of clinical trials. In total, F-CRIN represents a strike force of more than 1,400 professionals in clinical research. F-CRIN benefits from the support of several University Hospitals, Universities and Foundations.
For more information : https://www.fcrin.org/