Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000950066
Ethics application status
Approved
Date submitted
4/11/2010
Date registered
5/11/2010
Date last updated
5/11/2010
Type of registration
Prospectively registered

Titles & IDs
Public title
Fibrinolytic treatment of acute respiratory failure due to inflammatory lung injury
Scientific title
Fibrinolytic treatment of acute respiratory failure due to inflammatory lung injury to assess improvement in alveolar dead space and right ventricular function
Secondary ID [1] 253027 0
Not applicable
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
acute respiratory failure due to inflammatory lung injury 258588 0
Condition category
Condition code
Respiratory 258725 258725 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Administration of tissue plasminogen activator (t-PA) on one occasion.

Dose escalation study

The first 4 patients will receive

1. 10 mg bolus and 10 mg over 30 min.

The second 4 patients will receive

2. 10 mg bolus and 20 mg over 30 min.

The final 4 patients will receive

3. 10 mg bolus and 40 mg over 30 min.
Intervention code [1] 257553 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 259592 0
Phase 1 study

Alveolar dead space will be assessed using an expired breath carbon dioxide analyser
Timepoint [1] 259592 0
baseline and at 1 and 4 hours post t-pa
Primary outcome [2] 259593 0
pulmonary artery pressure and cardiac function will be assessed using echocardiology
Timepoint [2] 259593 0
baseline and at 1 and 4 hours post t-pa
Primary outcome [3] 259594 0
safety (bleeding) will be assessed by monitoring of the patient in the Intensive Care Unit for fall in Haemoglobin levels or clinical evidence of bleeding
Timepoint [3] 259594 0
in 24 hours following the t-pa
Secondary outcome [1] 266224 0
urinary albumin creatinine ratio will be assessed by analysing albumin and creatinine levels in the urine
Timepoint [1] 266224 0
baseline and at 1 and 4 hours post t-pa

Eligibility
Key inclusion criteria
Patients with acute respiratory failure due to an acute inflammatory insult.
Requiring positive pressure ventilation via an endo-tracheal tube.
Impaired oxygenation - arterial partial pressure of oxygen to inspire fraction of oxygen ratio (P/F) <300 mmHg.
At least one quadrant of pulmonary infiltrate present on CXR.
Enrolled within 24 hrs of developing all of these criteria.
Minimum age
15 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Known hypersensitivity to alteplase (t-PA)
Aspirin in the last week
Any therapeutic anti-coagulant therapy
Significant bleeding disorder within the past six months
Any history of brain or spinal injury including trauma, stroke, transient ischaemic attack, neoplasm, surgery, infection, aneurysm or intracranial bleed.
Uncontrolled hypertension, systolic blood pressure (BP) >185 mmHg or diastolic BP >110 mmHg.
Recent (within ten days) prolonged or traumatic cardiopulmonary resuscitation (> 2 minutes), obstetric delivery, organ biopsy, puncture of non-compressible blood vessel (e.g. subclavian vein), major surgery or significant trauma.
Documented ulcerative gastrointestinal disease during the last three months.
Arterial aneurysms, arterial/venous malformations.
Neoplasm with increased bleeding risk.
Bacterial endocarditis, pericarditis.
Acute pancreatitis.
Severe hepatic disease/ dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) or active hepatitis.
Age <18 or > 75
Pulmonary haemorrhage in previous 12 months
Major surgery planned over the next 2 days
Diabetic haemorrhagic retinopathy or other haemorrhagic ophthalmic conditions.
Unlikely to survive 24 hours
Platelet count below 80,000/mm3

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
not applicable
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
12/12/2010
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 258004 0
Self funded/Unfunded
Name [1] 258004 0
Barry Dixon
Country [1] 258004 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital
Address
Victoria Pde, Fitzroy, Victoria, 3065
Country
Australia
Secondary sponsor category [1] 257199 0
None
Name [1] 257199 0
Address [1] 257199 0
Country [1] 257199 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259999 0
St Vincent's Hospital Fitzroy, Victoria, 3065
Ethics committee address [1] 259999 0
41 Victoria Pde, Fitzroy, Victoria, 3065
Ethics committee country [1] 259999 0
Australia
Date submitted for ethics approval [1] 259999 0
Approval date [1] 259999 0
29/10/2010
Ethics approval number [1] 259999 0
1/10/0129

Summary
Brief summary
Inflammatory insults including pneumonia, sepsis, aspiration, trauma, prolonged hypotension, cardiac surgery and pancreatitis can cause lung damage. One mechanism by which inflammation mediates lung injury is through deposition of fibrin in the pulmonary microcirculation. This study will investigate if limiting fibrin deposition through administration of tissue plasminogen activator reduces lung damage.
Trial website
none
Trial related presentations / publications
none
Public notes

Contacts
Principal investigator
Name 31873 0
Address 31873 0
Country 31873 0
Phone 31873 0
Fax 31873 0
Email 31873 0
Contact person for public queries
Name 15120 0
Barry Dixon
Address 15120 0
ICU St.Vincent's Hospital 41 Victoria Pde, Melbourne, Victoria, 3065
Country 15120 0
Australia
Phone 15120 0
61 0439618815
Fax 15120 0
Email 15120 0
[email protected]
Contact person for scientific queries
Name 6048 0
Barry Dixon
Address 6048 0
ICU St.Vincent's Hospital 41 Victoria Pde, Fitzroy, Melbourne, Victoria, 3065
Country 6048 0
Australia
Phone 6048 0
61 0439618815
Fax 6048 0
Email 6048 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.