NCT03500939

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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
223

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Aug 2019

Typical duration for phase_2

Geographic Reach
5 countries

22 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 27, 2018

Completed
22 days until next milestone

First Posted

Study publicly available on registry

April 18, 2018

Completed
1.3 years until next milestone

Study Start

First participant enrolled

August 1, 2019

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 16, 2022

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 22, 2022

Completed
Last Updated

September 23, 2022

Status Verified

September 1, 2022

Enrollment Period

2.8 years

First QC Date

March 27, 2018

Last Update Submit

September 21, 2022

Conditions

Acute Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

  • ischemic core growth from baseline to 24 hours

    difference in ischemic core volume (in mL) from baseline to 24 hours; intention-to-treat (ITT) analysis

    from baseline to 24 (22 to 36) hours

Secondary Outcomes (29)

  • change in National Institutes of Health Stroke Scale (NIHSS) score from baseline to 24 hours

    from baseline to 24 ± 6 hours

  • survival

    5 ± 2 days, 90 ± 10 days after randomization

  • National Institutes of Health Stroke Scale score (NIHSS)

    20 ± 10 minutes, 4 hours ± 15 minutes, 24 ± 6 hours, 5 ± 2 days, 90 ± 10 days after randomization

  • modified Rankin Scale score (mRS)

    5 ± 2 days, 90 ± 10 days after randomization

  • Barthel Index (BI)

    5 ± 2 days, 90 ± 10 days after randomization

  • +24 more secondary outcomes

Study Arms (2)

Normobaric hyperoxygenation + standard of care

EXPERIMENTAL

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.

Drug: Medical oxygenOther: Standard of care

standard of care alone

ACTIVE COMPARATOR

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%.

Other: Standard of care

Interventions

Medical oxygenDRUG

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

Normobaric hyperoxygenation + standard of care
Standard of careOTHER

e.g. thrombectomy, thrombolysis

Normobaric hyperoxygenation + standard of carestandard of care alone

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • 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

You may not qualify if:

  • 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)
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (22)

UZ Gent

Ghent, Belgium

Location

AZ Groeninge Kortrijk

Kortrijk, Belgium

Location

KU Leuven

Leuven, Belgium

Location

CHU de Liège

Liernu, Belgium

Location

Helsinki University Hospital

Helsinki, Finland

Location

CHU de Grenoble

Grendelbruch, France

Location

CHU de Nancy

Nancy, France

Location

CHU de Nice

Nice, France

Location

Centre Hospitalier Saint Anne de Paris

Paris, France

Location

Fondation Ophtalmologique Adolphe de Rothschild

Paris, France

Location

Universitätsklinikum Essen

Essen, Germany

Location

Universitätsklinikum Gießen

Giessen, Germany

Location

Universitätsklinikum Eppendorf

Hamburg, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, Germany

Location

Ludwig-Maximilians-Universität München

München, Germany

Location

St. Lukas Klinik

Solingen, Germany

Location

University Hospital Tuebingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, Germany

Location

Fundacio Hospital Universitari Vall D'Hebron

Barcelona, Spain

Location

Hospital Universitari de Bellvitge

Barcelona, Spain

Location

HCU Valladolid

Valladolid, Spain

Location

Related Publications (1)

  • 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.

    PMID: 37515459DERIVED

Related Links

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

StrokeCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health CareQuality of Health CareHealth Services AdministrationHealth Care Quality, Access, and Evaluation

Study Officials

  • Sven Poli, MD

    University Hospital Tübingen

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 27, 2018

First Posted

April 18, 2018

Study Start

August 1, 2019

Primary Completion

May 16, 2022

Study Completion

August 22, 2022

Last Updated

September 23, 2022

Record last verified: 2022-09

Locations

BE(4)DE(9)ES(3)FI(1)FR(5)