Trial of Nebulized Heparin Versus Placebo for Inhalation Trauma (Hepburn)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor:
Collaborator:
Dutch Burns Foundation
Information provided by (Responsible Party):
Prof. Dr. Marcus J. Schultz, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01773083
First received: January 16, 2013
Last updated: June 24, 2014
Last verified: June 2014
  Purpose

The purpose of this international multi-center double-blind randomized placebo-controlled trial is to determine the effect of nebulized heparin, compared to placebo, on the number of ventilator-free days at day 28, in burn patients with confirmed inhalation trauma requiring mechanical ventilation.


Condition Intervention Phase
Inhalation Injury
Burn Injury
Drug: unfractionated heparin
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial Investigating the Efficacy and Safety of Nebulized Heparin Versus Placebo in Burn Patients With Inhalation Trauma (Hepburn)

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • Number of ventilator-free days at day 28 [ Time Frame: at day 28 ] [ Designated as safety issue: No ]
    The number of ventilator-free days is defined as the number of days a patient is breathing without assist of a ventilator during the first 28 days; thus, the patient must be free of mechanical ventilation for 24 hours to have one ventilator-free day; if after successful detubation the patient requires a reintubation due to a surgical procedure, this reintubation will not count as a ventilator day - however, the day(s) will be counted as ventilator day(s) if mechanical ventilation is prolonged after surgery due to respiratory insufficiency.


Secondary Outcome Measures:
  • Clinical outcome parameters [ Time Frame: daily or at day 28 and day 90 ] [ Designated as safety issue: No ]
    Clinical outcome parameters will include but not be restricted to: (a) length of stay (ICU and hospital); (b) mortality (28- and 90 days); (c) mortality (ICU and hospital); (d) daily Lung Injury Score (LIS); (e) daily Oxygenation Index (OI) ; (f) daily Sequential Organ Failure Assessment (SOFA)-scores ; (g) cumulative dosages of sedatives; (h) incidence of Ventilator-associated Pneumonia (VAP); (i) total number of bronchoscopy-guided cleaning of the larger airway

  • Laboratory outcome parameters [ Time Frame: Blood and lavage samples: on admission day and every other day for a maximum period of 14 days ] [ Designated as safety issue: No ]
    Levels of markers of coagulation and fibrinolysis in blood and lung lavage fluid, Levels of markers of inflammation in blood and lung lavage fluid, Biomarkers of lung injury in blood and lung lavage fluid

  • Safety parameters [ Time Frame: daily, for a maximum period of 28 days ] [ Designated as safety issue: Yes ]
    Safety parameters will include but not be restricted to: Occurrence of serious bleedings, any other transfusion of blood products - red cells and/or platelets and/or plasma, Confirmed Heparin induced thrombocytopenia, prolonged activated partial thromboplastin time (aPTT > 150 seconds)


Estimated Enrollment: 116
Study Start Date: October 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: unfractionated heparin
25.000 IU/5 ml, will be nebulized 4 hourly (i.e. 6 times daily)
Drug: unfractionated heparin
nebulized 6 times daily, daily dose 150.000 IU for the maximum duration of 14 days
Other Names:
  • unfractionated heparin sodium, EV Product Code: SUB02475MIG,
  • Marketing Authorisation number: RVG 01372
  • ATC codes: B01AB01
Placebo Comparator: placebo
Sterile sodium chloride (NaCl 0.9%, Pfizer), in 5 ml, will be nebulized every 4 hours (i.e. 6 times daily)
Drug: placebo
Placebo: Sterile saline nebulized 6 times daily for the maximum duration of 14 days
Other Name: sterile sodium chloride (NaCl 0.9%)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Informed consent
  • Age > 18 years
  • Need for invasive mechanical ventilation
  • Confirmed inhalation trauma (bronchoscopically)

Exclusion Criteria:

  • > 36 hours after trauma
  • Receiving invasive ventilation > 24 hours
  • Expected duration of mechanical ventilation < 24 hours
  • Chronic obstructive pulmonary disease GOLD stage III and IV
  • Any history of pulmonary hemorrhage in the past 3 months
  • Any history of significant bleeding disorder
  • Known allergy to heparin, including heparin-induced thrombocytopenia
  • Pregnancy or breast feeding
  • Unlikely to survive for > 72 hours
  • Total body surface area (TBSA) > 60%
  • Witnessed or proven aspiration (i.e., confirmed by bronchoscopy)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01773083

Contacts
Contact: Gerie J Glas, MD 00 31 20 5668222 g.j.glas@amc.uva.nl

Locations
Australia, Victoria
St Vincent's Hospital Not yet recruiting
Melbourne, Victoria, Australia, 3065
Contact: Barry Dixon, MD       barry.dixon@svhm.org.au   
Principal Investigator: Barry Dixon, MD         
Belgium
University Hospital, Gent Recruiting
Gent, Oost-Vlaanderen, Belgium, 9000
Contact: Kirsten         
Contact: Colpaert, MD, Dr.       kirsten.colpaert@ugent.be   
Principal Investigator: Kirsten Colpaert, MD, Dr.         
University Hospital Gasthuisberg - Leuven Recruiting
Leuven, Vlaams-Brabant, Belgium, 3000
Contact: Jan Muller, MD       jan.muller@uzleuven.be   
Principal Investigator: Jan Muller, MD         
Ziekenhuis Netwerk Antwerpen- Stuivenberg Recruiting
Antwerpen, Belgium, 2000
Contact: Manu Malbrain, MD, Dr.       Manu.Malbrain@zna.be   
Principal Investigator: Manu Malbrain, MD, Dr.         
Netherlands
Academic Medical Center Not yet recruiting
Amsterdam, Noord-Holland, Netherlands, 1105 AZ
Principal Investigator: Marcus J Schultz, Prof. Dr.         
Sub-Investigator: Koenraad F van der Sluijs, Dr.         
Sub-Investigator: Gerie J Glas, MD         
Sub-Investigator: Marcel M Levi, Prof. Dr.         
Sub-Investigator: Nicole P Juffermans, Dr. MD         
Red Cross Hospital, Beverwijk, the Netherlands Recruiting
Beverwijk, Noord-Holland, Netherlands, 1942 LE
Contact: Paul Knape, MD       pknape@rkz.nl   
Contact: David P Mackie, MD       sd.mackie@wxs.nl   
Principal Investigator: Paul Knape, MD         
Sub-Investigator: David P Mackie, MD         
Maasstad Hospital Recruiting
Rotterdam, Zuid-Holland, Netherlands, 3079 DZ
Contact: Barry Cleffken, MD       cleffkenb@maasstadziekenhuis.nl   
Principal Investigator: Barry Cleffken, MD         
Martini Hospital Recruiting
Groningen, Netherlands, 9728 NT
Contact: Bert G Loef, MD       b.loef@mzh.nl   
Principal Investigator: Bert G Loef, MD, Dr.         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Dutch Burns Foundation
Investigators
Principal Investigator: Marcus J Schultz, MD-PhD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  More Information

No publications provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof. Dr. Marcus J. Schultz, Prof. Dr., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01773083     History of Changes
Other Study ID Numbers: HepBurn, 2012-003289-42
Study First Received: January 16, 2013
Last Updated: June 24, 2014
Health Authority: the Netherlands: Central Committee on Research inv. Human Subjects (CCMO)
the Netherlands: Institutional Review Board Amsterdam
Belgium: Federal Agency for medicines and health products (FAGG)
Belgium: Institutional Review Board (Leuven, Ghent, Antwerp)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Inhalation trauma
pulmonary coagulopathy
heparin nebulization
mechanical ventilation

Additional relevant MeSH terms:
Calcium heparin
Heparin
Respiratory Aspiration
Respiration Disorders
Respiratory Tract Diseases
Pathologic Processes
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on October 19, 2014