A Phase Ib/II in Patients With Acute Ischemic Stroke
2021年8月30日 更新者：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.
研究概览
地位
完全的
条件
研究类型
介入性
注册 (实际的)
24
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
-
-
Arkansas
-
Little Rock、Arkansas、美国、72205
- University of Arkansas for Medical Sciences
-
-
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 80年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
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
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
有源比较器：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).
其他名称：
|
|
安慰剂比较：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).
|
|
有源比较器：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).
其他名称：
|
|
安慰剂比较：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).
|
|
有源比较器：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).
其他名称：
|
|
安慰剂比较：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).
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Maximum Tolerated Dose (MTD) of DDFPe Evaluated by Number of Dose Limiting Toxicities
大体时间：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.
|
12 hours after subjects have had a documented Acute Ischemic Stroke (AIS)
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
NIHSS Assessment
大体时间：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.
|
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.
|
|
Modified Rankin Scale (mRS)
大体时间：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.
|
mRS values were obtained on Day 7 or Day of Discharge, Day 30 and Day 90.
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
赞助
调查人员
- 首席研究员：William Culp, MD、University of Arkansas
- 首席研究员：Sanjeeva Onteddu, MD、University of Arkansas
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2017年2月1日
初级完成 (实际的)
2018年7月9日
研究完成 (实际的)
2018年7月9日
研究注册日期
首次提交
2016年11月10日
首先提交符合 QC 标准的
2016年11月14日
首次发布 (估计)
2016年11月15日
研究记录更新
最后更新发布 (实际的)
2021年9月24日
上次提交的符合 QC 标准的更新
2021年8月30日
最后验证
2021年8月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.