Inhalation InjuryPhase 3HepburnNCT01773083
Trial of Nebulized Heparin Versus Placebo for Inhalation Trauma
A Phase 3 study testing unfractionated heparin in people with Inhalation Injury and Burn Injury, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 8 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Inhalation Injury, Burn Injury
- What is being tested?
- unfractionated heparin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 8 sitesin 3 countries
- Study dates
- Oct 2013to Dec 2017
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent
- Age > 18 years
- Need for invasive mechanical ventilation
- Confirmed inhalation trauma (bronchoscopically)
Who cannot join
- > 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
Show all 11Show fewer
- 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)
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
Netherlands4 sites
Academic Medical Center
Amsterdam, North Holland, 1105 AZ
Red Cross Hospital, Beverwijk, the Netherlands
Beverwijk, North Holland, 1942 LE
Martini Hospital
Groningen, 9728 NT
Maasstad Hospital
Rotterdam, South Holland, 3079 DZ
Belgium3 sites
Ziekenhuis Netwerk Antwerpen- Stuivenberg
Antwerp, 2000
University Hospital, Gent
Ghent, Oost-Vlaanderen, 9000
University Hospital Gasthuisberg - Leuven
Leuven, Vlaams-Brabant, 3000
About this study
Official title: Randomized Controlled Trial Investigating the Efficacy and Safety of Nebulized Heparin Versus Placebo in Burn Patients With Inhalation Trauma (Hepburn)
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.
- Conditions
- Inhalation Injury, Burn Injury
- Being tested
- unfractionated heparin, placebo
- Keywords
- Inhalation trauma, pulmonary coagulopathy, heparin nebulization, mechanical ventilation
- Medical subject headings
- Burns
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
unfractionated heparinDrug
Also called unfractionated heparin sodium, EV Product Code: SUB02475MIG,, Marketing Authorisation number: RVG 01372, ATC codes: B01AB01
nebulized 6 times daily, daily dose 150.000 IU for the maximum duration of 14 days
placeboDrug
Also called sterile sodium chloride (NaCl 0.9%)
Placebo: Sterile saline nebulized 6 times daily for the maximum duration of 14 days
| Study group | Role | What they receive |
|---|---|---|
| unfractionated heparin | Experimental | 25.000 IU/5 ml, will be nebulized 4 hourly (i.e. 6 times daily) Receives: Drug: unfractionated heparin |
| placebo | Placebo comparator | Sterile sodium chloride (NaCl 0.9%, Pfizer), in 5 ml, will be nebulized every 4 hours (i.e. 6 times daily) Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at day 28
Secondary outcomes (3)
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
Measured: daily or at day 28 and day 90
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
Measured: Blood and lavage samples: on admission day and every other day for a maximum period of 14 days
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)
Measured: daily, for a maximum period of 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2013 (estimated)
- Study startOct 2013
- Primary completionOct 2016
- Study completionDec 2017
Why it stopped: insufficient recruitment of patients and high costs associated with the purchase and blinding of study medication
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Inhalation InjuryStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch Burns Foundation
- Responsible party
- Principal investigator, Prof. Dr. Marcus J. Schultz, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Marcus J Schultz, MD-PhD, Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01773083
- Sponsor's protocol ID
- HepBurn
- Other IDs
- 2012-003289-42
- Acronym
- Hepburn
- Status last verified
- Feb 2022
- First submitted
- 16 Jan 2013
- Last updated
- 16 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24661817
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial Investigating the Efficacy and Safety of Nebulized Heparin Versus Placebo in Burn Patients With Inhalation Trauma (Hepburn)
- ClinicalTrials.gov ID
- NCT01773083
- Acronym / sponsor ID
- Hepburn / HepBurn
- Conditions
- Inhalation Injury, Burn Injury
- Keywords
- Inhalation trauma, pulmonary coagulopathy, heparin nebulization, mechanical ventilation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient recruitment of patients and high costs associated with the purchase and blinding of study medication
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- Dutch Burns Foundation
- Study start
- Oct 2013
- Primary completion
- Oct 2016 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 23 Jan 2013 (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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| unfractionated heparin | Experimental | Drug: unfractionated heparin25.000 IU/5 ml, will be nebulized 4 hourly (i.e. 6 times daily) |
| placebo | Placebo comparator | Drug: placeboSterile sodium chloride (NaCl 0.9%, Pfizer), in 5 ml, will be nebulized every 4 hours (i.e. 6 times daily) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Informed consent
- Age > 18 years
- Need for invasive mechanical ventilation
- Confirmed inhalation trauma (bronchoscopically)
Key exclusion criteria (11 listed)
- > 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
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 |
|---|---|---|
| unfractionated heparinAlso: unfractionated heparin sodium, EV Product Code: SUB02475MIG,, Marketing Authorisation number: RVG 01372, ATC codes: B01AB01nebulized 6 times daily, daily dose 150.000 IU for the maximum duration of 14 days | Drug | unfractionated heparin |
| placeboAlso: sterile sodium chloride (NaCl 0.9%)Placebo: Sterile saline nebulized 6 times daily for the maximum duration of 14 days | Drug | placebo |
Primary outcome
Number of ventilator-free days at day 28
Time frame: 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.
3 secondary outcomes
Clinical outcome parameters
Time frame: daily or at day 28 and day 90
Laboratory outcome parameters
Time frame: Blood and lavage samples: on admission day and every other day for a maximum period of 14 days
Safety parameters
Time frame: daily, for a maximum period of 28 days
Results and safety
The study was stopped early (reason given: insufficient recruitment of patients and high costs associated with the purchase and blinding of study medication). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2022.
- Derived from this study: PubMed 24661817Glas 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.
- HEPBURN websiteLink provided by the sponsor.
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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.
Marcus J Schultz, MD-PhD principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing unfractionated heparin in people with Inhalation Injury and Burn Injury, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 8 sites in 3 countries.
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 4 inclusion and 11 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: stopped early, as of the sponsor's last update on 16 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Netherlands, Belgium, Australia. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 stopped early (reason given: insufficient recruitment of patients and high costs associated with the purchase and blinding of study medication). Results are not available in the source record.
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?
Number of ventilator-free days at day 28 (time frame: at day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01773083, which also lists 1 linked publication.
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 Feb 2022.