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

Primary Purpose

Inhalation Injury, Burn Injury

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
unfractionated heparin
placebo
Sponsored by
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Inhalation Injury focused on measuring Inhalation trauma, pulmonary coagulopathy, heparin nebulization, mechanical ventilation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • St Vincent's Hospital
  • University Hospital, Gent
  • University Hospital Gasthuisberg - Leuven
  • Ziekenhuis Netwerk Antwerpen- Stuivenberg
  • Academic Medical Center
  • Red Cross Hospital, Beverwijk, the Netherlands
  • Maasstad Hospital
  • Martini Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

unfractionated heparin

placebo

Arm Description

25.000 IU/5 ml, will be nebulized 4 hourly (i.e. 6 times daily)

Sterile sodium chloride (NaCl 0.9%, Pfizer), in 5 ml, will be nebulized every 4 hours (i.e. 6 times daily)

Outcomes

Primary Outcome Measures

Number of ventilator-free days at day 28
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
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
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
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)

Full Information

First Posted
January 16, 2013
Last Updated
February 14, 2022
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
Dutch Burns Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT01773083
Brief Title
Trial of Nebulized Heparin Versus Placebo for Inhalation Trauma
Acronym
Hepburn
Official Title
Randomized Controlled Trial Investigating the Efficacy and Safety of Nebulized Heparin Versus Placebo in Burn Patients With Inhalation Trauma (Hepburn)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Terminated
Why Stopped
insufficient recruitment of patients and high costs associated with the purchase and blinding of study medication
Study Start Date
October 2013 (undefined)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
Dutch Burns Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inhalation Injury, Burn Injury
Keywords
Inhalation trauma, pulmonary coagulopathy, heparin nebulization, mechanical ventilation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
unfractionated heparin
Arm Type
Experimental
Arm Description
25.000 IU/5 ml, will be nebulized 4 hourly (i.e. 6 times daily)
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Sterile sodium chloride (NaCl 0.9%, Pfizer), in 5 ml, will be nebulized every 4 hours (i.e. 6 times daily)
Intervention Type
Drug
Intervention Name(s)
unfractionated heparin
Other Intervention Name(s)
unfractionated heparin sodium, EV Product Code: SUB02475MIG,, Marketing Authorisation number: RVG 01372, ATC codes: B01AB01
Intervention Description
nebulized 6 times daily, daily dose 150.000 IU for the maximum duration of 14 days
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
sterile sodium chloride (NaCl 0.9%)
Intervention Description
Placebo: Sterile saline nebulized 6 times daily for the maximum duration of 14 days
Primary Outcome Measure Information:
Title
Number of ventilator-free days at day 28
Description
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.
Time Frame
at day 28
Secondary Outcome Measure Information:
Title
Clinical outcome parameters
Description
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
Time Frame
daily or at day 28 and day 90
Title
Laboratory outcome parameters
Description
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
Time Frame
Blood and lavage samples: on admission day and every other day for a maximum period of 14 days
Title
Safety parameters
Description
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)
Time Frame
daily, for a maximum period of 28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marcus J Schultz, MD-PhD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Vincent's Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
University Hospital, Gent
City
Gent
State/Province
Oost-Vlaanderen
ZIP/Postal Code
9000
Country
Belgium
Facility Name
University Hospital Gasthuisberg - Leuven
City
Leuven
State/Province
Vlaams-Brabant
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Ziekenhuis Netwerk Antwerpen- Stuivenberg
City
Antwerpen
ZIP/Postal Code
2000
Country
Belgium
Facility Name
Academic Medical Center
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Red Cross Hospital, Beverwijk, the Netherlands
City
Beverwijk
State/Province
Noord-Holland
ZIP/Postal Code
1942 LE
Country
Netherlands
Facility Name
Maasstad Hospital
City
Rotterdam
State/Province
Zuid-Holland
ZIP/Postal Code
3079 DZ
Country
Netherlands
Facility Name
Martini Hospital
City
Groningen
ZIP/Postal Code
9728 NT
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
24661817
Citation
Glas GJ, Muller J, Binnekade JM, Cleffken B, Colpaert K, Dixon B, Juffermans NP, Knape P, Levi MM, Loef BG, Mackie DP, Malbrain M, Schultz MJ, van der Sluijs KF. HEPBURN - investigating the efficacy and safety of nebulized heparin versus placebo in burn patients with inhalation trauma: study protocol for a multi-center randomized controlled trial. Trials. 2014 Mar 25;15:91. doi: 10.1186/1745-6215-15-91.
Results Reference
derived
Links:
URL
https://sites.google.com/site/hepburnstudy/
Description
HEPBURN website

Learn more about this trial

Trial of Nebulized Heparin Versus Placebo for Inhalation Trauma

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