Penumbral Rescue by Normobaric O2 Administration in Patients With Ischemic Stroke and Target Mismatch ProFile

NCT ID: NCT03500939

Last Updated: 2022-09-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 223 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-01
• Study Completion Date: 2022-08-22

Brief Summary

The main objective of the PROOF trial is to investigate efficacy and safety of normobaric hyperoxygenation (NBHO) as a neuroprotective treatment in patients with acute ischemic stroke due to large vessel occlusion likely to receive endovascular mechanical thrombectomy (TBY) in a randomized controlled clinical phase IIb trial.

Detailed Description

http://www.proof-trial.eu/

European Union's Horizon 2020 research and innovation programme grant 733379 (2016): Euro 5.8 Mio

Conditions

Acute Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Normobaric hyperoxygenation + standard of care

Normobaric hyperoxygenation (NBHO), i.e. inhalation of 100% oxygen at high flow (≥ 40 L/min) via a sealed non-rebreather face-mask with reservoir, or in case of intubation/ventilation for (study-independent) TBY, ventilation with an inspiratory oxygen fraction (FiO2) of 1.0. NBHO is started within 3 hours of stroke symptom onset (witnessed or last seen well) and within 20 minutes after end of baseline brain imaging and applied until the end of TBY procedure (defined by removal of guide catheter from sheath) or, in case TBY is not attempted, 4 hours after start of study treatment.

Group Type: EXPERIMENTAL

Medical oxygen

Intervention Type: DRUG

inhalation of 100% oxygen at high flow via a sealed non-rebreather face-mask with reservoir

Standard of care

Intervention Type: OTHER

e.g. thrombectomy, thrombolysis

standard of care alone

standard of care alone; oxygen supplementation if SpO2 ≤ 94% at 2 to 4 L/min via nasal cannula according to guidelines of the European Stroke Organisation (ESO), or in case of TBY-related intubation/ventilation, ventilation with an initial FiO2 of 0.3 to be gradually increased if SpO2 ≤ 94%.

Group Type: ACTIVE_COMPARATOR

Standard of care

Intervention Type: OTHER

e.g. thrombectomy, thrombolysis

Interventions

Medical oxygen

inhalation of 100% oxygen at high flow via a sealed non-rebreather face-mask with reservoir

Intervention Type: DRUG

Standard of care

e.g. thrombectomy, thrombolysis

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age: >= 18 years
• Acute anterior circulation ischemic stroke due to an LVO on CT or MR angiography, i.e. either terminal ICA with M1/carotid-T, proximal M1, distal M1 (distal to perforating branches), or M2/3 segment(s)
• If TBY is likely to be conducted* (*However, neither TBY nor IVT are a prerequisite for inclusion; patients not receiving TBY or IVT or both can be enrolled. Clinical treatment decisions should not delay study enrollment).
• NIHSS score of ≥ 6 at screening
• ASPECTS of 7-10 on NCCT or 6-10 on DWI-MRI
• CT or MR perfusion (whole-brain or minimal coverage ≥ 75 mm) prior to NBHO
• NBHO can be initiated within 6 hours of symptom onset (witnessed or last seen well) and within 30 minutes after last image of baseline brain imaging
• Pre-stroke mRS of 0 or 1
• Breastfeeding women must stop breastfeeding after randomization
• Own written informed consent is not obtained prior to study inclusion but has to be gained as soon as possible. Patients who are able to give consent will be informed about trial participation orally and may consent to or decline participation. Patients unable to give consent will be enrolled through a deferred consent procedure.

Exclusion Criteria

Neurological:

• TBY procedure initiated (groin puncture) prior to randomization
• Rapid major improvement in neurological status prior to randomization
• Any condition which precludes obtaining an accurate baseline NIHSS or outcome assessment (e.g. seizures, dementia, psychiatric or neuromuscular disease)
• Intracranial hemorrhage (except of cerebral microbleeds), intracranial tumor (except small meningioma), and/or intracranial arteriovenous malformation
• Intracranial aneurysm or prior stent implantation in the vascular territory (upstream and downstream) affected by qualifying LVO
• Suspected complete CCA occlusion, aortic dissection, cerebral vasculitis, septic embolism, or bacterial endocarditis
• Acute bilateral stroke or stroke in multiple vascular territories (except of clinically silent micro-lesions)

Respiratory:

• Known history of chronic pulmonary disease (e.g. COPD, pulmonary fibrosis, alveolitis or pneumonitis)
• Prior to enrolment, > 2 L/min oxygen required to maintain peripheral oxygen saturation ≥ 95%
• Acute respiratory distress that may, in the clinical judgment of the investigator, interfere with the study intervention
• Acute pneumonia, alveolitis or pneumonitis of viral, bacterial, fungal or any other etiology

Other:

• Clinical suspicion of acute myocardial infarction (e.g. acute chest pain)
• Baseline blood glucose of < 50 mg/dL (2.78 mmol) or > 400 mg/dL (22.20 mmol)
• Body temperature ≥ 38.0°C at screening
• History of severe allergy (more than rash) to contrast medium
• Current treatment with nitrofurantoin or amiodaron, paraquat poisoning, or history of treatment with bleomycin
• Pregnancy at screening, to be excluded (β-HCG in serum or urine) in all women ≤ 55 years except if surgically sterile; in women >55 years pregnancy must be excluded only in case of increased probability e.g. due to in-vitro fertilization
• Any co-existing or terminal disease (except qualifying stroke) with anticipated life expectancy of less than 6 months
• Any pre-existing condition that may, in the clinical judgment of the investigator, not allow safe participation in the study (e.g. alcohol or substance abuse, co-existing disease)
• Participation in another interventional (drug or device) study within the last four weeks
• Prior participation in the PROOF trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Coordination Centre for Clinical trials (KKS), 69120 Heidelberg, Germany

UNKNOWN

Sponsor Role: collaborator

European Clinical Research Infrastructure Network (ECRIN), 10559 Berlin, Germany

UNKNOWN

Sponsor Role: collaborator

CORE IMAGING LABORATORY: Eppdata GmbH, 22529 Hamburg, Germany

UNKNOWN

Sponsor Role: collaborator

CORE BIOMARKER LABORATORY: Fundatio Hospital Universitari Vall d'Hebron, 08035 Barcelona, Spain

UNKNOWN

Sponsor Role: collaborator

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sven Poli, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Tübingen

Locations

UZ Gent

Ghent, , Belgium

AZ Groeninge Kortrijk

Kortrijk, , Belgium

KU Leuven

Leuven, , Belgium

CHU de Liège

Liernu, , Belgium

Helsinki University Hospital

Helsinki, , Finland

CHU de Grenoble

Grendelbruch, , France

CHU de Nancy

Nancy, , France

CHU de Nice

Nice, , France

Centre Hospitalier Saint Anne de Paris

Paris, , France

Fondation Ophtalmologique Adolphe de Rothschild

Paris, , France

Universitätsklinikum Essen

Essen, , Germany

Universitätsklinikum Gießen

Giessen, , Germany

Universitätsklinikum Eppendorf

Hamburg, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Universitätsklinikum Schleswig-Holstein

Kiel, , Germany

Ludwig-Maximilians-Universität München

München, , Germany

St. Lukas Klinik

Solingen, , Germany

University Hospital Tuebingen

Tübingen, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Fundacio Hospital Universitari Vall D'Hebron

Barcelona, , Spain

Hospital Universitari de Bellvitge

Barcelona, , Spain

HCU Valladolid

Valladolid, , Spain

Countries

Belgium; Finland; France; Germany; Spain

References

Poli S, Mbroh J, Baron JC, Singhal AB, Strbian D, Molina C, Lemmens R, Turc G, Mikulik R, Michel P, Tatlisumak T, Audebert HJ, Dichgans M, Veltkamp R, Husing J, Graessner H, Fiehler J, Montaner J, Adeyemi AK, Althaus K, Arenillas JF, Bender B, Benedikt F, Broocks G, Burghaus I, Cardona P, Deb-Chatterji M, Cvikova M, Defreyne L, De Herdt V, Detante O, Ernemann U, Flottmann F, Garcia Guillamon L, Glauch M, Gomez-Exposito A, Gory B, Sylvie Grand S, Harsany M, Hauser TK, Heck O, Hemelsoet D, Hennersdorf F, Hoppe J, Kalmbach P, Kellert L, Kohrmann M, Kowarik M, Lara-Rodriguez B, Legris L, Lindig T, Luntz S, Lusk J, Mac Grory B, Manger A, Martinez-Majander N, Mengel A, Meyne J, Muller S, Mundiyanapurath S, Naggara O, Nedeltchev K, Nguyen TN, Nilsson MA, Obadia M, Poli K, Purrucker JC, Raty S, Richard S, Richter H, Schilte C, Schlemm E, Stohr L, Stolte B, Sykora M, Thomalla G, Tomppo L, van Horn N, Zeller J, Ziemann U, Zuern CS, Hartig F, Tuennerhoff J; PROOF investigators. Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial. Int J Stroke. 2024 Jan;19(1):120-126. doi: 10.1177/17474930231185275. Epub 2023 Aug 18.

Reference Type: DERIVED

PMID: 37515459 (View on PubMed)

Related Links

http://www.proof-trial.eu/

Related Info

Other Identifiers

2017-001355-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PROOF

Identifier Type: -

Identifier Source: org_study_id