Clinical trial NCT02963376: A Phase Ib/II in Patients With Acute Ischemic Stroke
Official title: A Phase Ib/II Dose-finding Study of DDFPe in Patients With Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ischemic Stroke
Lead sponsor: NuvOx LLC
Sponsor class: INDUSTRY
Collaborators: name: University of Arkansas
First posted: 2016-11-15
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Stroke is the fifth leading cause of death in the United States and is the leading cause of long term disability. Distinct geographic disparities in stroke mortality, with highest rates in the southeast United States including Arkansas, are known as the "stroke belt." There the average stroke mortality is ≈20% to 40% higher than the rest of the nation. Stroke is the leading cause of serious long-term disability. Between 2012 and 2030, disability and medical costs related to stroke are projected to triple, from $71.6 billion to $184.1 billion, with the majority of the projected increase in costs arising from those 65 to 79 years of age.

There are two main forms of stroke, ischemic and hemorrhagic. An ischemic stroke occurs in 85% of cases and is caused by cerebral vessel occlusion, obstructing blood flow to a portion of the brain. Currently, the only approved therapies for acute ischemic stroke are IV tissue plasminogen activator (tPA), a thrombolytic agent that clears the thrombus within the blood vessel, or intra-arterial catheter thrombectomy. Despite the availability of therapy, it reaches only approximately 7% of ischemic stroke victims in the United States5. Delay beyond the effective time window for therapy is a common reason for failure.

To reduce the devastating impact of stroke on individuals and society, the investigators continue to seek ways to improve functional recovery and limit ischemic damage in stroke patients. The potential neuroprotective agent, dodecafluoropentane emulsion (DDFPe) has recently shown strong positive effects in pre-clinical animal models of acute ischemic stroke6-11. Other perfluorocarbons have been tested in humans as potential neuroprotectants and blood substitutes yet none have been successful.


Eligibility criteria: Inclusion Criteria:

* Ages 18-80 years
* Diagnosis of AIS
* Body weight ≥ 45 kg
* NIHSS between 2 and 20
* Patient or legal authorized representative (LAR) must be willing and able to understand the study and provide written informed consent

Exclusion Criteria:

Currently pregnant or breastfeeding

* History of significantly impaired renal or hepatic function
* Hemorrhage or hemorrhagic stroke on CT scan
* Prior stroke, intracranial surgery, or major head trauma within three months prior to enrollment
* Pre-stroke modified Rankin Scale (mRS) ≥ 2
* Myocardial infarction within six (6) months prior to enrollment
* Unstable angina, New York Heart Association (NYHA) Class II or greater congestive heart failure
* Uncontrolled hypertension (SBP \> 180 and/or diastolic blood pressure (DBP) \> 110 mmHg)
* Known long QT syndrome or QTc \> 450 milliseconds (ms) in males and \> 470 ms in females
* Uncontrolled arrhythmia or history of clinically significant arrhythmia within the past six (6) months (except atrial fibrillation)
* Clinically significant chronic obstructive pulmonary disease (COPD) or other pulmonary condition that is not controlled by medication or requires oxygen frequently or continuously
* Pneumonia, bronchitis, or other acute respiratory disease
* Current anticoagulant therapy except for antiplatelet therapy (aspirin, NSAIDs) and prophylactic doses of low molecular weight heparin to prevent deep vein thrombosis. Note: tPA administered as part of subjects' therapy for AIS is allowed.
* History of allergic reaction attributed to compounds of similar chemical composition to DDFPe (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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of DDFPe Evaluated by Number of Dose Limiting Toxicities
timeFrame: 12 hours after subjects have had a documented Acute Ischemic Stroke (AIS)
Secondary outcomes:
measure: NIHSS Assessment
timeFrame: NIHSS scores were recorded at outside hospitals when appropriate and also at the study center as inside baseline NIHSS score. Repeat NIHSS scores were recorded at 2, 3.5, and 7.5 hours after drug injection and on discharge.
measure: Modified Rankin Scale (mRS)
timeFrame: mRS values were obtained on Day 7 or Day of Discharge, Day 30 and Day 90.
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
Study officials:
affiliation: University of Arkansas
name: William Culp, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Arkansas
name: Sanjeeva Onteddu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Culp WC, Onteddu SS, Brown A, Nalleballe K, Sharma R, Skinner RD, Witt T, Roberson PK, Marsh JD. Dodecafluoropentane Emulsion in Acute Ischemic Stroke: A Phase Ib/II Randomized and Controlled Dose-Escalation Trial. J Vasc Interv Radiol. 2019 Aug;30(8):1244-1250.e1. doi: 10.1016/j.jvir.2019.04.020.