COVID-19Phase 2/3INHALE-HEPNCT05184101
Inhaled Heparin for Hospitalised Patients With Coronavirus Disease 2019 (COVID-19)
A Phase 2/3 study testing Unfractionated Heparin in people with COVID-19, run by Australian National University at 1 site in Australia.
Trial summary
Investigator-initiated, multi-centre, randomised, open-label trial of nebulised heparin sodium in addition to standard care compared to standard care alone in hospitalised patients with COVID-19 infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Unfractionated Heparin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteAustralia
- Study dates
- Aug 2023to 1 Mar 2024
- Phase
- Phase 2/3
- 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
- Age 18 years or older
- Currently admitted to hospital
- There is a positive sample for COVID-19 within the past 14 days. The sample can be a nasal or pharyngeal swab, sputum, tracheal aspirate, bronchoalveolar lavage, or another sample from the patient
- Requiring oxygenation according to the modified ordinal clinical scale 4-5
Who cannot join
- Intubated and on mechanical ventilation, or requiring immediate intubation as per the treating clinician's assessment
- Heparin allergy or heparin-induced thrombocytopaenia
- Activated partial thromboplastin time (APTT) > 120 seconds, not due to anticoagulant therapy and does not correct with administration of fresh frozen plasma
- Platelet count < 20 x 10^9 per L within 48 hours of randomisation
- Pulmonary bleeding or uncontrolled bleeding within 48 hours of randomisation
- Known or suspected pregnancy
Show all 12Show fewer
- Acute brain injury that may result in long-term disability
- Myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. Guillain-Barre syndrome
- Treatment limitations in place, i.e. not for intubation, not for ICU admission
- Death is imminent or inevitable within 24 hours
- Clinician objection
- Participant consent declined
Trial locations and contacts
1 site in 1 country.
About this study
Official title: INHALEd Nebulised Unfractionated HEParin for the Treatment of Hospitalised Patients With COVID-19 (INHALE-HEP) Australia
Investigator-initiated, multi-centre, randomised, open-label trial of nebulised heparin sodium in addition to standard care compared to standard care alone in hospitalised patients with COVID-19 infection.
Read the detailed description
Heparin has been used as a medicine for over 75 years. It is used mostly as an anticoagulant (blood thinner), injected under the skin or infused into a vein to prevent or treat large blood clots.
Most patients who are eligible for this study are already receiving heparin administered under the skin or into a vein, and this treatment would continue after enrolment in the study, as determined by the treating doctors according to best practice.
In this study heparin is administered using a nebuliser. A nebuliser is a device that changes a fluid into a mist of tiny droplets so it can be easily breathed into the lungs. A nebuliser is a commonly used and effective way of giving medications that work in the lungs. Nebulised heparin is not currently a standard treatment, but there are good reasons to think it could help.
Lung infections, including COVID-19, cause the widespread formation of tiny blood clots in the small blood vessels and air sacs of the lungs, which make breathing difficult and lead to lung damage. Previous studies of patients with serious breathing problems due to pneumonia and other conditions found that nebulised heparin reduced the formation of small blood clots in the lungs, reduced the amount of injury to the lungs and hastened recovery with faster return to living at home. The virus that causes COVID-19 (the SARS-CoV-2 virus) has 'spikes' on its surface that enable it to attach to cells of the body and enter those cells. Another way that nebulised heparin might help is by sticking to these spikes on the virus and inhibiting the ability of the virus to enter the cells.
The main aim is to determine if nebulised heparin reduces the chance that a patient needs help with their breathing from a mechanical ventilator. Other aims are to determine if nebulised heparin increases the chances of surviving and of getting better quicker.
- Conditions
- COVID-19
- Being tested
- Unfractionated Heparin
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Unfractionated HeparinDrug
Also called Heparin
Heparin sodium will be administered as a nebulised aerosol dose of 25,000 IU heparin three times a day (TDS) via an Aerogen Solo (Aerogen, Ireland) vibrating mesh aerosol drug nebulizer.
| Study group | Role | What they receive |
|---|---|---|
| Nebulised heparin | Experimental | Participants assigned to 'nebulised heparin' will receive nebulised heparin in addition to the standard care required as determined by the treating team. Receives: Drug: Unfractionated Heparin |
| Standard care | No intervention | Participants assigned to 'standard care' will receive the standard care required as determined by the treating team and will not be treated with nebulised heparin. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intubation
The primary outcome is intubation (or death, for patients who died before intubation) before or at day 28 after randomisation.
Measured: 28 days
Secondary outcomes (3)
Mortality
Survival to hospital discharge censored at day 60
Measured: 60 days
Oxygenation
Daily ratio of oxygen saturation by pulse oximetry (SpO2) to the fraction of inspired oxygen (FiO2): (SpO2/FiO2 ratio, highest and lowest levels)
Measured: 28 days
Length of hospitalisation
Duration of hospital length of stay censored at day 60
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2022
- Study startAug 2023 (estimated)
- Primary completion1 Dec 2023 (estimated)
- Study completion1 Mar 2024 (estimated)
Why it stopped: COVID-19 hospitalisations limited in Australia, unable to recruit patients due to low numbers of hospitalisations.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- investigator-initiated, multi-centre, randomised, open-label trial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Australian National University
- Sponsor type
- University, hospital or other
- Collaborators
- The George Institute, St George Hospital, Australia, St Vincent's Hospital Melbourne, John Hunter Hospital, Royal North Shore Hospital
- Responsible party
- Principal investigator, Frank van Haren, Australian National University
- Investigators
- Frank MP van Haren, PhD, Principal investigator, Australian National University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05184101
- Sponsor's protocol ID
- INHALE-HEP Australia Version 3
- Acronym
- INHALE-HEP
- Status last verified
- Feb 2024
- First submitted
- 6 Jan 2022
- Last updated
- 26 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Planned international meta-trial see NCT04635241
Publications
van Haren FMP, Page C, Laffey JG, Artigas A, Camprubi-Rimblas M, Nunes Q, Smith R, Shute J, Carroll M, Tree J, Carroll M, Singh D, Wilkinson T, Dixon B. Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence. Crit Care. 2020 Jul 22;24(1):454. doi: 10.1186/s13054-020-03148-2.
PubMed 32698853van Haren FMP, Richardson A, Yoon HJ, Artigas A, Laffey JG, Dixon B, Smith R, Vilaseca AB, Barbera RA, Ismail TI, Mahrous RS, Badr M, De Nucci G, Sverdloff C, van Loon LM, Camprubi-Rimblas M, Cosgrave DW, Smoot TL, Staas S, Sann K, Sas C, Belani A, Hillman C, Shute J, Carroll M, Wilkinson T, Carroll M, Singh D, Page C. INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol and statistical analysis plan for an investigator-initiated international metatrial of randomised studies. Br J Clin Pharmacol. 2021 Aug;87(8):3075-3091. doi: 10.1111/bcp.14714. Epub 2021 Jan 19.
PubMed 33377218
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- INHALEd Nebulised Unfractionated HEParin for the Treatment of Hospitalised Patients With COVID-19 (INHALE-HEP) Australia
- ClinicalTrials.gov ID
- NCT05184101
- Acronym / sponsor ID
- INHALE-HEP / INHALE-HEP Australia Version 3
- Conditions
- COVID-19
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: COVID-19 hospitalisations limited in Australia, unable to recruit patients due to low numbers of hospitalisations.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Australian National UniversityUniversity, hospital or other
- Collaborators
- The George Institute, St George Hospital, Australia, St Vincent's Hospital Melbourne, John Hunter Hospital, Royal North Shore Hospital
- Study start
- Aug 2023 (estimated)
- Primary completion
- 1 Dec 2023 (estimated)
- Study completion
- 1 Mar 2024 (estimated)
- First posted
- 11 Jan 2022 (actual)
- 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.
Investigator-initiated, multi-centre, randomised, open-label trial of nebulised heparin sodium in addition to standard care compared to standard care alone in hospitalised patients with COVID-19 infection.
Detailed description
Heparin has been used as a medicine for over 75 years. It is used mostly as an anticoagulant (blood thinner), injected under the skin or infused into a vein to prevent or treat large blood clots.
Most patients who are eligible for this study are already receiving heparin administered under the skin or into a vein, and this treatment would continue after enrolment in the study, as determined by the treating doctors according to best practice.
In this study heparin is administered using a nebuliser. A nebuliser is a device that changes a fluid into a mist of tiny droplets so it can be easily breathed into the lungs. A nebuliser is a commonly used and effective way of giving medications that work in the lungs. Nebulised heparin is not currently a standard treatment, but there are good reasons to think it could help.
Lung infections, including COVID-19, cause the widespread formation of tiny blood clots in the small blood vessels and air sacs of the lungs, which make breathing difficult and lead to lung damage. Previous studies of patients with serious breathing problems due to pneumonia and other conditions found that nebulised heparin reduced the formation of small blood clots in the lungs, reduced the amount of injury to the lungs and hastened recovery with faster return to living at home. The virus that causes COVID-19 (the SARS-CoV-2 virus) has 'spikes' on its surface that enable it to attach to cells of the body and enter those cells. Another way that nebulised heparin might help is by sticking to these spikes on the virus and inhibiting the ability of the virus to enter the cells.
The main aim is to determine if nebulised heparin reduces the chance that a patient needs help with their breathing from a mechanical ventilator. Other aims are to determine if nebulised heparin increases the chances of surviving and of getting better quicker.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- investigator-initiated, multi-centre, randomised, open-label trial
| Arm | Type | Receives |
|---|---|---|
| Nebulised heparin | Experimental | Drug: Unfractionated HeparinParticipants assigned to 'nebulised heparin' will receive nebulised heparin in addition to the standard care required as determined by the treating team. |
| Standard care | No intervention | –Participants assigned to 'standard care' will receive the standard care required as determined by the treating team and will not be treated with nebulised heparin. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18 years or older
- Currently admitted to hospital
- There is a positive sample for COVID-19 within the past 14 days. The sample can be a nasal or pharyngeal swab, sputum, tracheal aspirate, bronchoalveolar lavage, or another sample from the patient
- Requiring oxygenation according to the modified ordinal clinical scale 4-5
Key exclusion criteria (12 listed)
- Intubated and on mechanical ventilation, or requiring immediate intubation as per the treating clinician's assessment
- Heparin allergy or heparin-induced thrombocytopaenia
- Activated partial thromboplastin time (APTT) > 120 seconds, not due to anticoagulant therapy and does not correct with administration of fresh frozen plasma
- Platelet count < 20 x 10^9 per L within 48 hours of randomisation
- Pulmonary bleeding or uncontrolled bleeding within 48 hours of randomisation
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: HeparinHeparin sodium will be administered as a nebulised aerosol dose of 25,000 IU heparin three times a day (TDS) via an Aerogen Solo (Aerogen, Ireland) vibrating mesh aerosol drug nebulizer. | Drug | Nebulised heparin |
Primary outcome
Intubation
Time frame: 28 days
The primary outcome is intubation (or death, for patients who died before intubation) before or at day 28 after randomisation.
3 secondary outcomes
Mortality
Time frame: 60 days
Oxygenation
Time frame: 28 days
Length of hospitalisation
Time frame: 60 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2024.
- Background: PubMed 32698853van Haren FMP, Page C, Laffey JG, Artigas A, Camprubi-Rimblas M, Nunes Q, Smith R, Shute J, Carroll M, Tree J, Carroll M, Singh D, Wilkinson T, Dixon B. Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence. Crit Care. 2020 Jul 22;24(1):454. doi: 10.1186/s13054-020-03148-2.
- Background: PubMed 33377218van Haren FMP, Richardson A, Yoon HJ, Artigas A, Laffey JG, Dixon B, Smith R, Vilaseca AB, Barbera RA, Ismail TI, Mahrous RS, Badr M, De Nucci G, Sverdloff C, van Loon LM, Camprubi-Rimblas M, Cosgrave DW, Smoot TL, Staas S, Sann K, Sas C, Belani A, Hillman C, Shute J, Carroll M, Wilkinson T, Carroll M, Singh D, Page C. INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol and statistical analysis plan for an investigator-initiated international metatrial of randomised studies. Br J Clin Pharmacol. 2021 Aug;87(8):3075-3091. doi: 10.1111/bcp.14714. Epub 2021 Jan 19.
- Individual participant dataSharing planned: Yes. Planned international meta-trial see NCT04635241
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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.
Frank MP van Haren, PhD principal investigator
Australian National University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Unfractionated Heparin in people with COVID-19, run by Australian National University at 1 site in Australia.
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 12 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: withdrawn, as of the sponsor's last update on 26 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 withdrawn before enrolling participants, so there are no results.
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?
Intubation (time frame: 28 days). 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 NCT05184101, which also lists 2 linked publications.
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 26 Feb 2024.