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NanO2 for Large Vessel Occlusion Stroke (PROVEN)

Primary Purpose

Ischemic Stroke

Status

Not yet recruiting

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Placebo

dodecafluoropentane emulsion (DDFPe)

About this trial

This is an interventional treatment trial for Ischemic Stroke focused on measuring perfusion, penumbra, mechanical thrombectomy, large vessel occlusion stroke

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Ages 18 to 90 years old, male or female
Diagnosis of LVO ischemic stroke
Pre-stroke mRS ≤ 2
NIHSS ≥ 6
Eligible for mechanical thrombectomy per local criteria
Subject or LAR must be willing and able to understand the study and provide written informed consent
Women of childbearing potential or men with child-bearing potential partners (unless vasectomized) must agree to use a highly effective method of birth control from study entry until 4 months after completing study therapy. Should a study participant or their partner become pregnant or suspect a pregnancy they should inform the treating study physician immediately

Exclusion Criteria:

> 12 hours since onset of stroke symptoms
Currently pregnant or breastfeeding
History of significantly impaired renal or hepatic function
Severe hemorrhage or severe hemorrhagic stroke on CT scan. Mild or moderate changes of Fisher Grade 1 or 2 subarachnoid hemorrhage are allowed as are hemorrhagic transformation changes of Grade HI-1 and HI-224,25
Unable to undergo a contrast brain perfusion scan with either MRI or CT
Pre-stroke mRS > 2 (See Appendix 3)
Unstable angina, NYHA Class II or greater congestive heart failure
Uncontrolled hypertension (Systolic BP ≥ 200 and/or Diastolic BP ≤ 120 mmHg)
Uncontrolled arrhythmia or history of clinically significant arrhythmia within the past six (6) months (except atrial fibrillation)
Current acute or chronic lung disease requiring supplemental chronic or intermittent oxygen therapy.
History of allergic reaction attributed to compounds of similar chemical composition to NanO2TM (see Investigator's Brochure).
Subject has received any investigational drug within thirty (30) days prior to enrollment into the study
Inability to comply with the study procedures
History or evidence of any other clinically significant condition that, in the opinion of the investigator, might pose a safety risk to subjects or interfere with study procedures, evaluation, or completion

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

NanO2

Arm Description

Placebo which appears the same as the treatment to investigators, clinicians and subjects.

A milky white intravenous injectable emulsion

Outcomes

Primary Outcome Measures

National Institutes of Health Stroke Scale and Modified Rankin Scale

Both are established and accepted measures of stroke. NIHSS has a scale from 0 to 42 and mRS has a scale from 0 to 6. In both cases, a lower score represents less brain damage.

Secondary Outcome Measures

Full Information

NCT ID

NCT05389748

First Posted

May 17, 2022

Last Updated

May 20, 2022

Sponsor

NuvOx LLC

Collaborators

University of Arkansas, Stanford University, Washington Regional Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT05389748

Brief Title

NanO2 for Large Vessel Occlusion Stroke

Acronym

PROVEN

Official Title

Phase IIb to Restore Oxygen in Large Vessel Occlusion Patients En Route for MT Using NanO2

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

April 1, 2023 (Anticipated)

Primary Completion Date

April 1, 2025 (Anticipated)

Study Completion Date

September 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

NuvOx LLC

Collaborators

University of Arkansas, Stanford University, Washington Regional Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

A two stage phase 2 study with an interim analysis to provide evidence that subjects provided with early administration of NanO2 who are located at small rural spoke hospitals and identified with large vessel occlusion ischemic strokes as well as viable penumbra prior to transfer to larger hub hospitals and who continue dosing NanO2 until revascularization is achieved by intravenous alteplase and/or mechanical thrombectomy, will experience stroke recovery by shifting ischemic brain tissue to normal tissue pO2 environments.

Detailed Description

Recent stroke studies have shown that subjects with Large Vessel Occlusion (LVO) ischemic stroke have rapid infarct growth. The investigators hypothesize that early administration of NanO2 in subjects with LVO ischemic stroke will maintain the viability of tissue in the penumbra until revascularization is achieved with intravenous alteplase and/or mechanical thrombectomy (MT). The rationale for administering the dose evaluated is: The dose level is within the levels already tested in animals and humans.5-13 Volunteers received two IV bolus doses of 0.35 mL/kg of activated NanO2TM 24 hours apart and brain cancer subjects received daily doses of up to 0.17 mL/kg of inactivated NanO2TM.18 A completed trial of NanO2TM in acute ischemic stroke at the University of Arkansas had the high dose cohort receive three doses of NanO2 (0.17 mL/kg) 90 minutes apart and demonstrated safety at this dose. Therapeutic reduction in stroke damage has been observed at dose levels of 0.1 mL/kg in rabbits.5-9,12 Since drug effects tend to correlate with body surface area/weight, one would predict that a dose of approximately 0.03 mL/kg should be effective in humans compared to rabbits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ischemic Stroke

Keywords

perfusion, penumbra, mechanical thrombectomy, large vessel occlusion stroke

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo which appears the same as the treatment to investigators, clinicians and subjects.

Arm Title

NanO2

Arm Type

Active Comparator

Arm Description

A milky white intravenous injectable emulsion

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Subjects with large vessel occlusion stroke eligible for mechanical thrombectomy are randomized to placebo in association with standard of care

Intervention Type

Biological

Intervention Name(s)

dodecafluoropentane emulsion (DDFPe)

Intervention Description

Subjects with large vessel occlusion stroke eligible for mechanical thrombectomy are randomized to DDFPe in association with standard of care

Primary Outcome Measure Information:

Title

National Institutes of Health Stroke Scale and Modified Rankin Scale

Description

Both are established and accepted measures of stroke. NIHSS has a scale from 0 to 42 and mRS has a scale from 0 to 6. In both cases, a lower score represents less brain damage.

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Ages 18 to 90 years old, male or female Diagnosis of LVO ischemic stroke Pre-stroke mRS ≤ 2 NIHSS ≥ 6 Eligible for mechanical thrombectomy per local criteria Subject or LAR must be willing and able to understand the study and provide written informed consent Women of childbearing potential or men with child-bearing potential partners (unless vasectomized) must agree to use a highly effective method of birth control from study entry until 4 months after completing study therapy. Should a study participant or their partner become pregnant or suspect a pregnancy they should inform the treating study physician immediately Exclusion Criteria: > 12 hours since onset of stroke symptoms Currently pregnant or breastfeeding History of significantly impaired renal or hepatic function Severe hemorrhage or severe hemorrhagic stroke on CT scan. Mild or moderate changes of Fisher Grade 1 or 2 subarachnoid hemorrhage are allowed as are hemorrhagic transformation changes of Grade HI-1 and HI-224,25 Unable to undergo a contrast brain perfusion scan with either MRI or CT Pre-stroke mRS > 2 (See Appendix 3) Unstable angina, NYHA Class II or greater congestive heart failure Uncontrolled hypertension (Systolic BP ≥ 200 and/or Diastolic BP ≤ 120 mmHg) Uncontrolled arrhythmia or history of clinically significant arrhythmia within the past six (6) months (except atrial fibrillation) Current acute or chronic lung disease requiring supplemental chronic or intermittent oxygen therapy. History of allergic reaction attributed to compounds of similar chemical composition to NanO2TM (see Investigator's Brochure). Subject has received any investigational drug within thirty (30) days prior to enrollment into the study Inability to comply with the study procedures History or evidence of any other clinically significant condition that, in the opinion of the investigator, might pose a safety risk to subjects or interfere with study procedures, evaluation, or completion

12. IPD Sharing Statement

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NanO2 for Large Vessel Occlusion Stroke

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