The HEPALI Study|
|- candidate number||2846|
|- NTR Number||NTR1109|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||30-okt-2007|
|- Secondary IDs||N/A VU medical center|
|- Public Title||The HEPALI Study|
|- Scientific Title||The effects of inhaled heparin on pulmonary coagulation activation and vascular permeability in mechanically ventilated patients with Acute Lung Injury / Acute Respiratory Distress Syndrome.|
|- hypothesis||Nebulization of heparin will have a beneficial effect on pulmonary coagulopathy, reflected in reduction of pulmonary coagulation activation in the broncho-alveolar lavage fluid, and will decrease pulmonary vascular permeability reflected in a reduction of the PLI.|
|- Healt Condition(s) or Problem(s) studied||Acute Lung Injury, Acute Respiratory Distress Syndrome|
|- Inclusion criteria||Inclusion criteria
All patients being intubated and mechanically ventilated in the ICU, who meet the International Consensus Criteria of ALI or ARDS:|
1. Informed consent;
2. Age: 18-80 years;
3. Recent onset of ALI or ARDS (i.e. <48 hrs).
|- Exclusion criteria||1. Acute bleeding at any site;|
2. Increased risk of bleeding:
Thrombocytes < 50 x 109/L
aPTT > 60 sec
PT > 20 sec, or INR > 1.7;
3. Within 24 hours after major surgery;
4. Proven or clinically suspected heparin induced thrombocytopenia;
5. Hemorrhagic diathesis;
6. Heparin allergy;
7. Pregnancy or breast feeding.
|- mec approval received||no|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jan-2008|
|- planned closingdate||1-jan-2009|
|- Target number of participants||28|
|- Interventions||Nebulization of heparin (100,000 IU) or placebo every 8 hrs during 24 hrs. Before the first and after the last nebulization bronchoscopy will be performed to obtain bronchoalveolar lavage fluid of both the affected and the non-affected lung. At the same time measurement of the PLI will be performed.|
|- Primary outcome||1. TATc in BAL fluid;|
|- Secondary outcome||1. LIS;|
2. In blood: TF, TFPI activity, TFPI antigen, Factor VII/VIIa, protein C / activated protein C, prothrombin fragment 1.2, TATc, endogenous thrombin potential, fibrin monomers, soluble thrombomodulin, PAPc, PAI;
3. In BAL fluid: TF, TFPI activity, TFPI antigen, Factor VII/VIIa, protein C / activated protein C, prothrombin fragment 1.2, TATc, endogenous thrombin potential, fibrin monomers, soluble thrombomodulin, PAPc, PAI;
4. Occurrence and severity of bleeding events.
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| A.D. Cornet|
|- CONTACT for SCIENTIFIC QUERIES|| A.D. Cornet|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|VU University Medical Center|
|- Brief summary||Introduction|
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are potentially lethal conditions, responsible for a considerable amount of admissions to the Intensive Care Unit (ICU) and for which, at present, only supportive care is available.
Pulmonary edema, as a result of increased pulmonary vascular permeability caused by proinflammatory changes, together with pulmonary coagulopathy, resulting in alveolar fibrin deposition and disturbed fibrin turnover, are the hallmarks of ALI/ARDS. The alveolar fibrin deposition is in part comparable to the intravascular deposition of fibrin in patients with sepsis and disseminated intravascular coagulation and may be aggravated by mechanical ventilation.
Based on a substantial body of evidence, both in vitro and in vivo, there is rationale to intervene in the pulmonary coagulopathy with anticoagulants in general, and with heparin in particular, in order to attenuate lung injury. Delivering heparin directly into the pulmonary compartment may attenuate fibrin depositions more effectively than systemic administration of heparin, while reducing the risk of bleeding as a result of systemic anticoagulant effects. In sheep, nebulization of heparin has been found to be beneficial. Furthermore, the nebulization of heparin to the lower respiratory tract is feasible and safe. In pediatric patients with inhalation injuries, heparin nebulization significantly reduced mortality.
With a bedside radionuclide method the pulmonary leak index (PLI) can be obtained as a measure of vascular leakage. The PLI is an ideal instrument to measure effects of therapy on pulmonary vascular leakage, since serial measurements can be performed.
Hence, nebulization of heparin may have a beneficial effect on pulmonary coagulopathy and may subsequently decrease pulmonary vascular permeability.
In a prospective, open-label, placebo controlled, randomised clinical trial we will evaluate the effects of heparin nebulization in mechanically ventilated patients with ALI/ARDS.
1. To determine whether nebulization of heparin decreases coagulation activation in the pulmonary compartment (i.e. BAL fluid);
2. to determine whether nebulization of heparin decreases pulmonary vascular permeability.
|- Main changes (audit trail)|
|- RECORD||30-okt-2007 - 23-apr-2008|
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