PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke (Precious)
Every year, 1.3 million Europeans have a stroke. 20 to 35% of the patients die in the first month after stroke, and around one third remain dependent on the help of others. The annual costs for stroke care in Europe are estimated at € 64.1 billion. Mainly in the first days after stroke onset, patients are at risk of complications, such as infections and fever. These complications are strongly and independently associated with a higher risk of death or dependency.
PRECIOUS is a pragmatic, randomised, open clinical trial with blinded outcome assessment in 1,500 patients with acute stroke aged 66 years or older. The trial studied whether pharmacological prevention of infections and fever, and early management of dysphagia, will reduce the risk of death, poor functional outcome, and poor quality of life, and lead to reductions in the costs of stroke care throughout Europe. Patients were randomised using a factorial design to preventive treatment with ceftriaxone, paracetamol, and/or metoclopramide, or to ‘standard care’ alone. This simple, safe, and generally available treatment strategy has the potential to lead to an annual reduction of over 25,000 elderly Europeans being dead or dependent as a result of stroke, at very low costs.
The project was coordinated by Dr Van der Worp (UMC Utrecht) and started on 1 June 2015. A total of 6 million Euros has been awarded to the consortium to run the trial over seven years. PRECIOUS received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634809, and ends November 2022.
More information on Precious research can be found at https://www.precious-trial.eu/ .
Interview with Jeroen de Jonge, Neurology Resident, UMC Utrecht
SAFE: If you were to explain the project’s aim to a person without any medical background, what would you say?
The PRECIOUS trial stands for ‘PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke’. This medical trial is an EU-funded Horizon 2020 collaborative research project dedicated to look for ways to improve the recovery of stroke patients aged 66 years or older. After a stroke, patients can have complications, such as fever or a pneumonia. Patients who have a complication after stroke, usually recovery worse than patients without a complication. Normally, the complications are treated when symptoms become obvious. Fever is treated with paracetamol, nausea and vomiting with metoclopramide, and infections are treated with antibiotics. In this trial, we give the treatments before symptoms occur, to test if we can prevent the complications and thereby improve recovery.
SAFE: What types of partner do you need to carry out a project like this?
The setting-up, conduct and management of a trial like PRECIOUS involves many different partners and organizations. PRECIOUS is carried out in about 80 hospitals in 9 European countries. Before starting medical research with patients, it has to be approved by regulatory authorities, which assess if your trial is useful, safe, ethical and feasible. In every participating hospital, there is a dedicated doctor who helps with setting-up the trial. However, sometimes the rules and regulations are so complex, that a specialized research organization is involved to help this process.
During the course of the trial, several partners are involved, each with a specific task. For example, there is a safety team that collects information about potential side effects of the drugs, to keep an eye on the safety of the treatments. A different team designs an electronic data system, which is a safe online platform where local investigators can fill in patient data. Also, there is a team that visits the hospitals periodically, to monitor if the trial is being performed according to the rules. Also, at the end of the trial, a lot of information is gathered, and we need a statistical team to process all the information to determine if the treatments are effective. However, these are just a few examples, and you need a lot of partners to carry out such as project.
SAFE: Can you briefly describe your role in the project?
My role as a trial manager is to oversee all processes related to PRECIOUS on a day-to-day basis. The work is very broad and consists, for example, the general management of the trial, support with obtaining regulatory approvals, setting-up participating hospitals, including patients into the trial, and answering questions of local investigators about patient recruitment, data collection or follow-up of patients.
SAFE: What (if any) are the difficulties with carrying out the work?
Obtaining regulatory approvals in different countries and hospitals requires a lot of paperwork and bureaucratic tasks. This process takes a lot of time. Off course, it is very important that research is assessed very carefully before it can start, but sometimes specific aspects of the research are being assessed multiple times. It takes a lot of time before the research can actually start, and that is sometimes challenging.
SAFE: What personally attracted you to be in this project?
Stroke is the world’s second largest cause of death and the third cause of long-term disability.
Many patients suffer from a stroke on a daily basis. However, there are still limited treatment options available. Because of medical research, there has been considerable progress in the treatment of stroke and new effective treatment options have become available in the past decade. The possibility support research that looks for new ways to treat stroke is what personally attracts me in this project.
SAFE: When this project ends, what do you expect to change, i.e. how it will reflect on stroke treatment?
We hope to find a simple, safe and effective treatment strategy for patients who have had a stroke, which can prevent the development of complications and improve recovery after stroke.
INVOLVING STROKE SURVIVORS IN CLINICAL TRIALS
Interview with a PRECIOUS clinical trial patient, Utrecht
SAFE: Why did you think it was important to take part in the PRECIOUS clinical trial?
PATIENT: For us (me and my family) the stroke diagnosis and treatment was a nerve-racking experience, however we think research is important, and this trial did sound like a potential beneficial treatment.
SAFE: Did you have any fears or reservations before making the decision?
PATIENT: Not really no, the trial was clearly explained by the physician, and we recognised the importance of it, so we wanted to take part.
SAFE: Do you think participation has benefited you? (eg did it make you feel more positive about the future, more confident, happier?)
PATIENT: At the moment, I am doing really well. I have been improving steadily the last three months. I hope off course, part of this is due to my participating in this trial, because that would mean the treatment could work.
SAFE: What are your hopes after taking part?
PATIENT: I hope it provides valuable information for the researchers, to improve care for patients with stroke. I have recovered quite well, but I know from other stories this is not always the case.
SAFE: What would you say to someone who is considering participating in a trial?
PATIENT: Do consider it! Research and clinical trials are usually well thought-out, and it could potentially be beneficial for you or future patients
SAFE: If you were asked to take part in a trial now, would the pandemic influence your decision
PATIENT: Of course, at this moment everything is influenced by the pandemic. It would off course depend on the type of trial, but yes I would still participate in a trial.