A Phase Ib/II in Patients With Acute Ischemic Stroke
30 augustus 2021 bijgewerkt door: NuvOx LLC
A Phase Ib/II Dose-finding Study of DDFPe in Patients With Acute Ischemic Stroke
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.
Studie Overzicht
Toestand
Voltooid
Conditie
Studietype
Ingrijpend
Inschrijving (Werkelijk)
24
Fase
- Fase 1
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Arkansas
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Little Rock, Arkansas, Verenigde Staten, 72205
- University of Arkansas for Medical Sciences
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar tot 80 jaar (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
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
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verdrievoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Actieve vergelijker: 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.
|
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).
Andere namen:
|
|
Placebo-vergelijker: 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.
|
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).
|
|
Actieve vergelijker: 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.
|
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).
Andere namen:
|
|
Placebo-vergelijker: 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.
|
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).
|
|
Actieve vergelijker: 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.
|
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).
Andere namen:
|
|
Placebo-vergelijker: 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.
|
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).
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Maximum Tolerated Dose (MTD) of DDFPe Evaluated by Number of Dose Limiting Toxicities
Tijdsspanne: 12 hours after subjects have had a documented Acute Ischemic Stroke (AIS)
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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.
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12 hours after subjects have had a documented Acute Ischemic Stroke (AIS)
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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NIHSS Assessment
Tijdsspanne: 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.
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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.
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Modified Rankin Scale (mRS)
Tijdsspanne: mRS values were obtained on Day 7 or Day of Discharge, Day 30 and Day 90.
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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.
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mRS values were obtained on Day 7 or Day of Discharge, Day 30 and Day 90.
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Medewerkers
Onderzoekers
- Hoofdonderzoeker: William Culp, MD, University of Arkansas
- Hoofdonderzoeker: Sanjeeva Onteddu, MD, University of Arkansas
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
1 februari 2017
Primaire voltooiing (Werkelijk)
9 juli 2018
Studie voltooiing (Werkelijk)
9 juli 2018
Studieregistratiedata
Eerst ingediend
10 november 2016
Eerst ingediend dat voldeed aan de QC-criteria
14 november 2016
Eerst geplaatst (Schatting)
15 november 2016
Updates van studierecords
Laatste update geplaatst (Werkelijk)
24 september 2021
Laatste update ingediend die voldeed aan QC-criteria
30 augustus 2021
Laatst geverifieerd
1 augustus 2021
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 205529
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Ja
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Nee
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .