Community Research and Development Information Service - CORDIS

H2020

PRECIOUS Report Summary

Project ID: 634809
Funded under: H2020-EU.3.1.

Periodic Reporting for period 1 - PRECIOUS (PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke)

Reporting period: 2015-06-01 to 2016-11-30

Summary of the context and overall objectives of the project

The central objective of the PRECIOUS (PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke) study is to assess whether prevention of complications in the first days after stroke onset - using simple, cheap, existing, and generally available interventions - reduces the risk of death or dependency and improves quality of life in elderly patients with acute stroke. PRECIOUS will assess whether a pharmacological strategy to prevent the most common complications in elderly patients with acute stroke is more effective at reducing the risk of death and improving functional outcome than current clinical practice - recommended in guidelines - of waiting until these complications are manifest before initiating treatment.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In collaborative effort of all partners, a PRECIOUS study protocol has been developed that reflects ethical principles that have their origin in the Declaration of Helsinki, and that is consistent with guidelines for Good Clinical Practice of the International Conference on Harmonisation (ICH-GCP) and all applicable regulatory requirements. The study has been registered with the European Union Drug Regulating Authorities Clinical Trials (EudraCT) under number 2015-003179-32, and with the International Standard Randomised Controlled Trial Number (ISRCTN) registry as ISRCTN82217627.
A National Coordinator Agreement (NCA) has been concluded between the study sponsor UMC and National Coordinators (NCs), and a model Clinical Trial Agreement (CTA) has been developed in which the Sponsor UMC and each individual site confirm to agree to the specific terms and conditions relevant for the conduct of the clinical trial. Of note, both the NCA and CTA differ between NCs and study sites because each have their own specific rules, regulations, and traditions. The process of concluding these agreements is supported by the legal department at UMC.
Standard Operating Procedures (SOPs) have been developed to facilitate recruitment into the trial and to support trial treatment and follow-up. So far, SOPs are available for training of NCs and local Principal Investigators; training of study monitors; site initiation visits; and use of the Investigator Site File.
The Data Management Department of the Julius Center at UMC has built a web-based treatment allocation service that is available 24/7. Treatment allocation is stratified by country and includes the following minimisation factors for balance in baseline characteristics: age (66 – 75 years vs. > 75 years); sex (male vs. female); stroke type (ischaemic stroke vs. intracerebral haemorrhage); stroke severity (NIHSS 6 – 12 vs. > 12); and diabetes mellitus (yes vs. no). Investigators have the opportunity to censor a specific randomisation arm in a specific patient before randomisation, for example in case of an allergy to one of the investigational medicinal products (IMPs).
SOPs and working instructions for the eCRF are available in an online manual at the secured area of the PRECIOUS website www.precious-trial.eu. An instruction video for the users at the participating sites is also available at the PRECIOUS website to explain the use of the randomisation and eCRF website. Training of the national coordinators and PIs is also provided at an individual or small-group level before the start of PRECIOUS at each participating site.
With the intent to achieve a harmonised and rapid approval of the trial in the participating countries, UMC has requested a ‘voluntary harmonised procedure’ (VHP) for PRECIOUS for Estonia, Germany, Hungary, Italy, and the United Kingdom. VHP approval was granted on 18 January 2016. Within a few weeks, this approval was confirmed by the CAs in Germany and the UK, but the CAs in the three other countries needed an additional review process before approval was granted. CA approval in the Netherlands and Norway was obtained via separate review processes, and the process of obtaining approval in Poland and Greece is underway.
Following the approval by the CAs, UMC and the NCs have sought approval of the National RECs in each of the participating countries. In 7 of the 9 countries, this has been obtained.
In each of the countries, the approval by the CA and national REC is followed by local hospital management approval at each individual site. We anticipated that this could be obtained within 2 months for most of the sites, but because of bureaucratic hurdles or additional review of the study details this takes on average at least 4 months. Importantly, these delays are largely beyond our control because these are related to internal processes at the study sites. So far, full approval by the local hospital management has been obtained for just three sites in the Netherlands, but in each of the seven countries with CA and national REC approval, local hospital management approvals are expected within the following weeks to months. We expect that the majority of approvals will have been obtained by month 24 of the project, but because of the delay in Poland and Greece submission of the ‘all approval package’ (D1.4) with approvals from all ethics committees and national competent authorities of all study sites once the last approval has been received is expected to be delayed from month 24 to month 30.
After REC approval of UMC in February 2016, and successful site initiation in March, 7 patients have been included up to last 30 November. Because none of the other sites had yet been initiated by that date, these are the only inclusions in the trial so far. As mentioned above, we expect approval and initiation of the other sites in the 7 countries with CA and national REC approval shortly, followed by a steep increase in recruitment.
A Safety Desk for PRECIOUS has been established and is responsible for safety monitoring (pharmacovigilance) of the clinical trial in PRECIOUS including collection of all SAE reports reported by the Investigators to the safety desk. Reported SAEs are checked for completeness and expectedness, documented and coded according to MedDRA. Furthermore, the Safety Desk is responsible for the monitoring all safety issues and a continuous benefit-risk assessment. Once a year the Development Safety Update Report (DSUR) is developed and submitted to the responsible contact point for submission to the Ethics Committees and Competent Authorities.
An independent Data and Safety Monitoring Board (DSMB) and an Ethics Advisory Board were also formed.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

One socio economic impact is the large reduction in the costs for stroke care throughout Europe. Much of the costs of stroke care are related to the occurrence of complications. These not only prolong hospital stays, but it is also much more expensive, for instance, to treat an established pneumonia in a single patient than to administer preventive antibiotics for four days in several patients. However, the largest reduction in costs will be related to improved functional outcomes, requiring fewer and shorter admissions to rehabilitation centres and chronic nursing facilities. Assuming average annual costs for care in a chronic nursing facility of € 30 000, 26 000 fewer patients admitted to such a facility on a yearly basis, and on average two years of admission to such a facility, this would lead to an annual reduction in costs for admission to a chronic nursing facility of 1,56 billion euros.

Related information

Record Number: 198423 / Last updated on: 2017-05-19
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