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A Phase Ib/II in Patients With Acute Ischemic Stroke

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02963376
Recruitment Status : Completed
First Posted : November 15, 2016
Results First Posted : September 24, 2021
Last Update Posted : September 24, 2021
Sponsor:
Collaborator:
University of Arkansas
Information provided by (Responsible Party):
NuvOx LLC

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.


Condition or disease Intervention/treatment Phase
Ischemic Stroke Drug: 0.05 mL/kg DDFPe Drug: 0.05 mL/kg Placebo Drug: 0.10 mL/kg DDFPe Drug: 0.10 mL/kg Placebo Drug: 0.17 mL/kg DDFPe Drug: 0.17 mL/kg Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Dose-finding Study of DDFPe in Patients With Acute Ischemic Stroke
Actual Study Start Date : February 1, 2017
Actual Primary Completion Date : July 9, 2018
Actual Study Completion Date : July 9, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ischemic Stroke

Arm Intervention/treatment
Active Comparator: 0.05 mL/kg DDFPe
This study is a randomized, placebo controlled, blinded escalating dose study designed to determine the maximum tolerated dose to intravenous administration of DDFPe. At each of the three dose levels 0.10, 0.17 mL/kg) six subjects will receive DDFPe and two will receive placebo.
Drug: 0.05 mL/kg DDFPe
Prior to injection, DDFPe will be prepared by pharmacy staff. DDFPe will be administered based on weight. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. DDFPe dosage volume in cc for 0.05 mL/kg based on patient body weight in kilograms (kg).
Other Name: Dodecafluoropentane emulsion (DDFPe), NanO2TM

Placebo Comparator: 0.05 mL/kg Placebo
This study is a randomized, placebo controlled, blinded escalating dose study designed to determine the maximum tolerated dose to intravenous administration of DDFPe. At each of the three dose levels 0.10, 0.17 mL/kg) six subjects will receive DDFPe and two will receive placebo.
Drug: 0.05 mL/kg Placebo
Prior to injection, the placebo will be prepared by pharmacy staff. The placebo will be administered based on weight at designated doses Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. The placebo dosage volume in cc for 0.05 mL/kg is based on patient body weight in kilograms (kg).

Active Comparator: 0.10 mL/kg DDFPe
This study is a randomized, placebo controlled, blinded escalating dose study designed to determine the maximum tolerated dose to intravenous administration of DDFPe. At each of the three dose levels 0.10, 0.17 mL/kg) six subjects will receive DDFPe and two will receive placebo.
Drug: 0.10 mL/kg DDFPe
Prior to injection, DDFPe will be prepared by pharmacy staff. DDFPe will be administered based on weight at designated doses. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. DDFPe dosage volume in cc for 0.10 mL/kg based on patient body weight in kilograms (kg).
Other Name: Dodecafluoropentane emulsion (DDFPe), NanO2TM

Placebo Comparator: 0.10 mL/kg Placebo
This study is a randomized, placebo controlled, blinded escalating dose study designed to determine the maximum tolerated dose to intravenous administration of DDFPe. At each of the three dose levels 0.10, 0.17 mL/kg) six subjects will receive DDFPe and two will receive placebo.
Drug: 0.10 mL/kg Placebo
Prior to injection, the placebo will be prepared by pharmacy staff. The placebo will be administered based on weight at designated doses. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. The placebo dosage volume in cc for 0.10 mL/kg is based on patient body weight in kilograms (kg).

Active Comparator: 0.17 mL/kg DDFPe
This study is a randomized, placebo controlled, blinded escalating dose study designed to determine the maximum tolerated dose to intravenous administration of DDFPe. At each of the three dose levels 0.10, 0.17 mL/kg) six subjects will receive DDFPe and two will receive placebo.
Drug: 0.17 mL/kg DDFPe
Prior to injection, DDFPe will be prepared by pharmacy staff. DDFPe will be administered based on weight at designated doses. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. DDFPe dosage volume in cc for 0.17 mL/kg based on patient body weight in kilograms (kg).
Other Name: Dodecafluoropentane emulsion (DDFPe), NanO2TM

Placebo Comparator: 0.17 mL/kg Placebo
This study is a randomized, placebo controlled, blinded escalating dose study designed to determine the maximum tolerated dose to intravenous administration of DDFPe. At each of the three dose levels 0.10, 0.17 mL/kg) six subjects will receive DDFPe and two will receive placebo.
Drug: 0.17 mL/kg Placebo
Prior to injection, the placebo will be prepared by pharmacy staff. The placebo will be administered based on weight at designated doses. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. The placebo dosage volume in cc for 0.17 mL/kg is based on patient body weight in kilograms (kg).




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of DDFPe Evaluated by Number of Dose Limiting Toxicities [ Time Frame: 12 hours after subjects have had a documented Acute Ischemic Stroke (AIS) ]
    The primary objective of this study is to establish the Maximum Tolerated Dose (MTD) of DDFPe given intravenously at intervals of 90 ± 10 minutes x 3 doses within 12 hours after subjects have had a documented Acute Ischemic Stroke (AIS). The algorithm for determining the MTD is based on the number of subjects who experience a Dose Limiting Toxicity (DLT) in each cohort, as defined in the clinical protocol. If three or more subjects who received DDFPe in an 8 subject cohort experience a DLT, the MTD will be determined to have been exceeded and further enrollment in the cohort as well as dose escalation will stop.


Secondary Outcome Measures :
  1. NIHSS Assessment [ Time Frame: 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. ]
    The NIH Stroke Scale (NIHSS) is an assessment tool that provides a quantitative measure of stroke-related neurologic deficit. The NIHSS is a 15-item neurologic examination. Ratings for each item are scored on a 3- to 5-point scale with 0 as normal. Scores range from 0 to 42, with higher scores indicating greater severity.

  2. Modified Rankin Scale (mRS) [ Time Frame: mRS values were obtained on Day 7 or Day of Discharge, Day 30 and Day 90. ]
    The modified Rankin Scale is a measure of the degree of disability in patients who have had a stroke with 0 being no symptoms at all to 6 being death. Thus, a higher score indicates greater severity.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02963376


Locations
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United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
NuvOx LLC
University of Arkansas
Investigators
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Principal Investigator: William Culp, MD University of Arkansas
Principal Investigator: Sanjeeva Onteddu, MD University of Arkansas
  Study Documents (Full-Text)

Documents provided by NuvOx LLC:
Additional Information:
Publications of Results:
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Responsible Party: NuvOx LLC
ClinicalTrials.gov Identifier: NCT02963376    
Other Study ID Numbers: 205529
First Posted: November 15, 2016    Key Record Dates
Results First Posted: September 24, 2021
Last Update Posted: September 24, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Stroke
Ischemic Stroke
Cerebral Infarction
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia
Infarction
Necrosis