Acute Respiratory Distress SyndromePhase 1NCT00431379
Treatment of Acute Respiratory Distress Syndrome With Tenecteplase: A Dose Escalation Pilot Study
A Phase 1 study testing Tenecteplase in people with Acute Respiratory Distress Syndrome, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
The pathogenesis of ARDS appears to be from damage to the alveolar-capillary barrier, which is composed of the microvascular endothelium and the alveolar epithelium. This damage may occur from direct or indirect lung injury. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- What is being tested?
- Tenecteplase
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2007to Dec 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to provide written informed consent and comply with study assessments for full duration of the study by family member.
- Patient-related considerations - See exclusion criteria
- Disease-related considerations - ARDS is indicated by respiratory failure of acute onset, bilateral lung infiltrates, PaO2/Fi02 <200 mmHg,pulmonary artery wedge pressure < 18 mmHg, and need for a ventilator. (If the wedge pressure is >18, the patient is excluded from this study).
- Only acute stage ARDS patients will be enrolled in the study. This is defined by patients with ARDS for <1 week.
- Other considerations
- Satisfactory recruitment and cooperation
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- A signed informed consent document
- No participation in another clinical and/or observational trial
- No previous participation in this study
- Not a prisoner or otherwise in custody and not institutionalized for mental incompetence.
- Patients with major trauma will only be included 5 days after trauma has occurred.
Who cannot join
- Bleeding - active internal bleeding
- History of cerebrovascular accident
- Intracranial neoplasm, arteriovenous malformation, or aneurysm or acute trauma
- Known bleeding diathesis
- Severe uncontrolled HTN
- Thrombin time over 2 times laboratory normal
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- Prothrombin time or partial thromboplastin time > 2 times normal
- Fibrinogen <100
- Platelets <100
- Creatine >2.0
- Liver function tests > 2 times normal
- History of coagulopathy, ulcer, or stroke
- Systolic blood pressure >180, diastolic blood pressure >110
- History of fibrinolytic use within one month prior to treatment
- History of diabetic retinopathy
- Pregnancy, pregnancy will be ruled out in women of childbearing age by urine test.
- Obstetric delivery or intracranial injury within one month prior to treatment
- Major trauma, major surgery, or CPR within 5 days or minor surgery or minor trauma within 2 days. The classification of major or minor is made by attending physician.
- Patients undergoing non-operative management of liver, spleen, and kidney trauma.
- Aspirin therapy >650mg q day
- Epidural or spinal catheter within 5 days.
- Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, and subacute bacterial endocarditis.
- Over the age of 75 years
- Patients on Xigris
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment of Acute Respiratory Distress Syndrome With Tenecteplase: A Dose Escalation Pilot Study: Phase I
The pathogenesis of ARDS appears to be from damage to the alveolar-capillary barrier, which is composed of the microvascular endothelium and the alveolar epithelium. This damage may occur from direct or indirect lung injury. The mechanism of injury to the alveolar capillary barrier appears to be through neutrophil-mediated injury, pro-inflammatory cytokines, ventilator-induced lung injury with alveolar over distention and abnormalities of the coagulation system. This results in blood clot formation in the microcirculation of the lung. Thrombolytics can dissolve blood clots and result in increased blood flow to the organs. This treatment may benefit ARDS patients, thus the purpose of this study.
Hardaway, et al.studied the effects of thrombolytics on ARDS in pigs. The experimental group showed improved oxygenation and survival as compared to controls. There was no bleeding complications noted with this therapy. Dr. Hardaway followed this animal study with a phase I clinical trial involving 20 patients with ARDS. The patients were treated with IV streptokinase or urokinase. Nineteen of the 20 patients showed an increase in PA02 after thrombolytic therapy. There were no significant bleeding complications in patients that were critically ill on ventilators.
We propose an additional phase I pilot study to evaluate the effectiveness and safety of Tenecteplase for the treatment of ARDS. Unlike the other fibrinolytics studied in this disease state, Tenecteplase, is more fibrin specific and has increased resistance to plasminogen activator inhibitor (PAI-I) at greater levels than other available fibrinolytics. We have chosen an experimental dose escalation trial design of tenecteplase that has demonstrated initial safety trends in a Phase I acute ischemic stroke trial. The initial dose is 0.1 mg/kg IV and will increase to 0.2 mg/kg, 0.3 mg/kg, with a final cohort of patients receiving 0.4 mg/kg. Drug administration will be a single dose bolus in each cohort. Advancement of dose will occur if safety is not in question in the previous cohort. We hope this will provide an acceptable benefit risk ratio as the mortality of ARDS is approximately 30 - 60%. All patients will be closely monitored for any change in clotting parameters and signs of bleeding. Tenecteplase will be administered via a peripheral IV as described in the package insert.
Read the detailed description
- Treatment of acute respiratory distress syndrome with tenecteplase, a dose escalation pilot study: phase I
- The study sample size will be 20 patients. The 20 patients will be divided into 4 groups with 5 patients in each group or cohort. The first cohort will received 0.1mg/kg of tenecteplase as a bolus via peripheral IV as described by the package insert and will be closely monitored for safety and efficacy. If there are no adverse events associated with tenecteplase, the second cohort of patients will be enrolled and will receive 0.2 mg/kg of tenecteplase IV bolus. If there are no safety issues, we will proceed with the next cohort at 0.3 mg/kg with a final cohort of patients receiving 0.4 mg/kg of tenecteplase IV bolus. Advancement of dose will occur if safety is not in question in the previous cohort.
- Tenecteplase will be given as a bolus via peripheral IV as described by package insert.
- Treatment will be initiated after informed consent is obtained and only >12 hrs after any subcutaneous Heparin has been stopped and >12 hrs after placement of a pulmonary artery catheter, central line or arterial line. Only patients meeting criteria for ARDS (see inclusion criteria) will be considered for the study.
- Pretreatment assessment: We will obtain informed consent, demographic data, physical examination and medical history, vital signs, PT, PTT, INR, ABG, hemoglobin hematocrit, liver enzymes, cardiac enzymes, creatinine, fibrinogen, fibrin split products, platelets, urine pregnancy test, EKG, chest x-ray, cardiac profile from Swan-Ganz catheter and ventilator settings before treatment begins.
- Assessment during treatment: Blood samples will be taken every 6 hours for 24 hours and analyzes for PT, PTT, INR, fibrinogen, fibrin split products, platelets, hemoglobin, and hematocrit. Arterial blood gas samples will be taken at hour 1, 2, 3, and every six hours until 24 hours post-injection. Cardiac profile, vital signs and ventilator settings will be monitored at hour 1, 2, 3, and every six hours until 24 hours post-infusion. Adverse events will be monitored every hour for 24 hours.
- Follow-up assessment: 72 hours post treatment physical exam, vital signs, weight, adverse events, cardiac profile, ventilator settings, PT, PTT, INR, fibrinogen, fibrin split products, platelets, ABG, hemoglobin and hematocrit, liver enzymes, cardiac enzymes, creatinine, EKG and chest x-ray will be obtained. Thirty days post treatment physical exam, vital signs, weight, mortality, adverse events will be followed.
- Patients will be monitored for signs of clinical bleeding.
- Conditions
- Acute Respiratory Distress Syndrome
- Being tested
- Tenecteplase
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TenecteplaseDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival to Discharge
Safety Analysis of Bleeding Complications
Secondary outcomes (5)
Improved Pa02/Fi02 ratio
Improved cardiac profile
Incidence of organ failure
Decreased ventilator days
Decreased ICU days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2007 (estimated)
- Study startFeb 2007
- Primary completionNov 2008
- Study completionDec 2008
Why it stopped: drug has expired, no enrollments in study. Company pulled funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Dennis W. Ashley, MD, FACS, Principal investigator, Medical Center of Central GADebra M Kitchens, RN, CEN, Study chair, Medical Center of Central Georgia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00431379
- Sponsor's protocol ID
- H0605329
- Status last verified
- Nov 2013
- First submitted
- 2 Feb 2007
- Last updated
- 16 Oct 2024
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Acute Respiratory Distress Syndrome With Tenecteplase: A Dose Escalation Pilot Study: Phase I
- ClinicalTrials.gov ID
- NCT00431379
- Acronym / sponsor ID
- H0605329
- Conditions
- Acute Respiratory Distress Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: drug has expired, no enrollments in study. Company pulled funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Feb 2007
- Primary completion
- Nov 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 5 Feb 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The pathogenesis of ARDS appears to be from damage to the alveolar-capillary barrier, which is composed of the microvascular endothelium and the alveolar epithelium. This damage may occur from direct or indirect lung injury. The mechanism of injury to the alveolar capillary barrier appears to be through neutrophil-mediated injury, pro-inflammatory cytokines, ventilator-induced lung injury with alveolar over distention and abnormalities of the coagulation system. This results in blood clot formation in the microcirculation of the lung. Thrombolytics can dissolve blood clots and result in increased blood flow to the organs. This treatment may benefit ARDS patients, thus the purpose of this study.
Hardaway, et al.studied the effects of thrombolytics on ARDS in pigs. The experimental group showed improved oxygenation and survival as compared to controls. There was no bleeding complications noted with this therapy. Dr. Hardaway followed this animal study with a phase I clinical trial involving 20 patients with ARDS. The patients were treated with IV streptokinase or urokinase. Nineteen of the 20 patients showed an increase in PA02 after thrombolytic therapy. There were no significant bleeding complications in patients that were critically ill on ventilators.
We propose an additional phase I pilot study to evaluate the effectiveness and safety of Tenecteplase for the treatment of ARDS. Unlike the other fibrinolytics studied in this disease state, Tenecteplase, is more fibrin specific and has increased resistance to plasminogen activator inhibitor (PAI-I) at greater levels than other available fibrinolytics. We have chosen an experimental dose escalation trial design of tenecteplase that has demonstrated initial safety trends in a Phase I acute ischemic stroke trial. The initial dose is 0.1 mg/kg IV and will increase to 0.2 mg/kg, 0.3 mg/kg, with a final cohort of patients receiving 0.4 mg/kg. Drug administration will be a single dose bolus in each cohort. Advancement of dose will occur if safety is not in question in the previous cohort. We hope this will provide an acceptable benefit risk ratio as the mortality of ARDS is approximately 30 - 60%. All patients will be closely monitored for any change in clotting parameters and signs of bleeding. Tenecteplase will be administered via a peripheral IV as described in the package insert.
Detailed description
- Treatment of acute respiratory distress syndrome with tenecteplase, a dose escalation pilot study: phase I
- The study sample size will be 20 patients. The 20 patients will be divided into 4 groups with 5 patients in each group or cohort. The first cohort will received 0.1mg/kg of tenecteplase as a bolus via peripheral IV as described by the package insert and will be closely monitored for safety and efficacy. If there are no adverse events associated with tenecteplase, the second cohort of patients will be enrolled and will receive 0.2 mg/kg of tenecteplase IV bolus. If there are no safety issues, we will proceed with the next cohort at 0.3 mg/kg with a final cohort of patients receiving 0.4 mg/kg of tenecteplase IV bolus. Advancement of dose will occur if safety is not in question in the previous cohort.
- Tenecteplase will be given as a bolus via peripheral IV as described by package insert.
- Treatment will be initiated after informed consent is obtained and only >12 hrs after any subcutaneous Heparin has been stopped and >12 hrs after placement of a pulmonary artery catheter, central line or arterial line. Only patients meeting criteria for ARDS (see inclusion criteria) will be considered for the study.
- Pretreatment assessment: We will obtain informed consent, demographic data, physical examination and medical history, vital signs, PT, PTT, INR, ABG, hemoglobin hematocrit, liver enzymes, cardiac enzymes, creatinine, fibrinogen, fibrin split products, platelets, urine pregnancy test, EKG, chest x-ray, cardiac profile from Swan-Ganz catheter and ventilator settings before treatment begins.
- Assessment during treatment: Blood samples will be taken every 6 hours for 24 hours and analyzes for PT, PTT, INR, fibrinogen, fibrin split products, platelets, hemoglobin, and hematocrit. Arterial blood gas samples will be taken at hour 1, 2, 3, and every six hours until 24 hours post-injection. Cardiac profile, vital signs and ventilator settings will be monitored at hour 1, 2, 3, and every six hours until 24 hours post-infusion. Adverse events will be monitored every hour for 24 hours.
- Follow-up assessment: 72 hours post treatment physical exam, vital signs, weight, adverse events, cardiac profile, ventilator settings, PT, PTT, INR, fibrinogen, fibrin split products, platelets, ABG, hemoglobin and hematocrit, liver enzymes, cardiac enzymes, creatinine, EKG and chest x-ray will be obtained. Thirty days post treatment physical exam, vital signs, weight, mortality, adverse events will be followed.
- Patients will be monitored for signs of clinical bleeding.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Ability to provide written informed consent and comply with study assessments for full duration of the study by family member.
- Patient-related considerations - See exclusion criteria
- Disease-related considerations - ARDS is indicated by respiratory failure of acute onset, bilateral lung infiltrates, PaO2/Fi02 <200 mmHg,pulmonary artery wedge pressure < 18 mmHg, and need for a ventilator. (If the wedge pressure is >18, the patient is excluded from this study).
- Only acute stage ARDS patients will be enrolled in the study. This is defined by patients with ARDS for <1 week.
- Other considerations
Key exclusion criteria (24 listed)
- Bleeding - active internal bleeding
- History of cerebrovascular accident
- Intracranial neoplasm, arteriovenous malformation, or aneurysm or acute trauma
- Known bleeding diathesis
- Severe uncontrolled HTN
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenecteplase | Drug | – |
Primary outcome
Survival to Discharge
Safety Analysis of Bleeding Complications
5 secondary outcomes
Improved Pa02/Fi02 ratio
Improved cardiac profile
Incidence of organ failure
Decreased ventilator days
Decreased ICU days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dennis W. Ashley, MD, FACS principal investigator
Medical Center of Central GA
Debra M Kitchens, RN, CEN study chair
Medical Center of Central Georgia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tenecteplase in people with Acute Respiratory Distress Syndrome, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 16 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival to Discharge. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2024.