Penumbral Rescue by Normobaric O=O Administration in Patients With Ischaemic Stroke and Target Mismatch ProFile: A Phase II Proof-of-Concept Trial

Project Information

PROOF

Grant agreement ID: 733379

DOI

10.3030/733379

Project closed

EC signature date 12 December 2016

Start date 1 January 2017

End date 30 June 2023

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost

€ 5 247 102,54

EU contribution

€ 5 246 831,94

Coordinated by

EBERHARD KARLS UNIVERSITAET TUEBINGEN
Germany

Periodic Reporting for period 5 - PROOF (Penumbral Rescue by Normobaric O=O Administration in Patients With Ischaemic Stroke and Target Mismatch ProFile: A Phase II Proof-of-Concept Trial)

Reporting period: 2023-01-01 to 2023-06-30

Summary of the context and overall objectives of the project

An ischaemic stroke is the most common type of stroke and a leading cause of mortality and morbidity in the world. The arteries that supply the brain with blood become clogged by clots. This kills the cells at the centre of the stroke and puts those nearby at great risk. The longer the brain suffers from oxygen and blood deficiency, the more serious the consequences, and the more brain tissue will die. Emergency treatment must therefore get rid of the blocked arteries as quickly as possible.
Within PROOF twelve clinical centres in eight European countries will test whether the consequences of stroke can be reduced by rapidly applying high-dose oxygen therapy.
The high-dose oxygen therapy is very simple and low-cost. The patient, after having been diagnosed with an ischemic stroke after their scan, wears a mask through which they inhale almost pure oxygen at a flow of 40 litres per minute. This keeps the oxygen content in the blood as high as it can be.
The aim is to ensure that the surrounding brain tissue at risk, which will have less oxygen but is not yet dead, is stabilized by the high oxygen content coming in. This continues until the clot is removed and the blood circulation is improved again. The treatment therefore aims at the so-called “shadow zones” of the stroke, sometimes called the “rescue zones”. These may include the entire stroke area in some patients.
PROOF is the first trial to thoroughly investigate high-dose oxygenation in stroke patients. If it proves that the brain can be saved by this, it could also bring great benefits to patients who are not near a clinic where stroke can be treated and who have longer access times to emergency care.

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

The main work performed in the fourth period of the project was to facilitate the recruitment as well as the preparation of the trial infrastructure in all participating European PROOF centers as well as the initiation of the Swiss study centers that received ethical approval for study participation within this period.

Main results achieved in period 4:
- Increasing numbers of patient enrolment to a sufficient level
- All regulatory and ethical approvals obtained
- Further revision of the eCRF
- Revision of worksheets to simplify the enrolment of patients for the study sites and to improve the process of data generation
- Update of all training materials
- Regular Newsletter
- Online-Consortium-Meetings and Board-Meetings
- Conducting Interim Analyses

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)

It was foreseen that PROOF could create a scale of impacts comprising:
• Improvement of health and quality of life for stroke patients,
• Scientific impacts for the researchers and clinicians working in the field - the PROOF trial results will be published in a peer reviewed journal with high impact (e.g. Neurology or higher)
• Healthcare impact for clinicians and rehabilitation professionals treating stroke patients – NBHO treatment will generate better treatment and rehabilitation outcomes, and
• Socio-economic impact on the health care system – improved patient outcomes will reduce healthcare costs and will also benefit society through early return of people with stroke to work
After termination of the study due to futility we need to wait for the results of the final analyses to check whether there are impacts still valid respectively how we need to change them in any way.

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