Covid19Phase 2/3INHALE-HEPNCT04635241
Inhaled Heparin for Hospitalised COVID-19 Patients
A Phase 2/3 study testing Unfractionated heparin in people with Covid19, run by Australian National University at 5 sites in 3 countries.
Trial summary
This meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled trials and early phase studies. Individual studies will be conducted in multiple countries, including Australia, the UK, the USA, Ireland, Argentina, Brazil and Egypt. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Unfractionated heparin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 485 participants
- Where
- 5 sitesin 3 countries
- Study dates
- 1 Jun 2020to 18 Jan 2025
- 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
- Patients admitted to hospital with COVID-19
- No immediate requirement for mechanical ventilation (points 3-5 on the WHO ordinal scale)
- Age equal to or greater than 18
- Able to provide informed consent
Who cannot join
- Pregnant women
- Known allergy to Heparin
- Participant in another clinical trial that is not approved for joint enrollment.
- APTT> 120 seconds, not due to anticoagulant therapy.
- Platelet count <20 x 109 per L
- Lung bleeding.
Show all 9Show fewer
- Uncontrolled bleeding
- Advanced neurological impairment
- Advanced oncological disease
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
Indonesia3 sites
RS Universitas Indonesia
Depok
RSUP Dr Cipto Mangunkusumo
Jakarta
RSUD Dr Moewardi
Surakarta
About this study
Official title: INHALEd Unfractionated HEParin for the Treatment of Hospitalised Patients With COVID-19 Meta-trial
This meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled trials and early phase studies. Individual studies will be conducted in multiple countries, including Australia, the UK, the USA, Ireland, Argentina, Brazil and Egypt.
Adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, will be randomised to inhaled nebulised heparin or standard care for up to 21 days or until the patient has no respiratory symptoms. All studies will collect a minimum core dataset. The primary outcome for the meta-trial is the proportion of patients who receive invasive mechanical ventilation censored at day 28. Individual studies may have specific outcome measures in addition to the core set.
- Conditions
- Covid19
- 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
Inhaled nebulised 6 hourly
| Study group | Role | What they receive |
|---|---|---|
| Inhaled heparin | Experimental | Inhaled nebulised unfractionated heparin in addition to standard care Dose 25,000 IU every 6 hours for up to 21 days Receives: Drug: Unfractionated heparin |
| Standard care | No intervention | Standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intubation rate
Proportion of patients requiring invasive mechanical ventilation
Measured: Day 28
Secondary outcomes (2)
WHO ordinal scale COVID19
Number of patients showing 1 or 2 point worsening on the ordinal scale
Measured: Day 7
Oxygenation
Daily ratio of partial pressure of oxygen to FiO2 (PaO2/FiO2)
Measured: Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2020
- Study start1 Jun 2020
- Primary completion1 Nov 2023
- Study completion18 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies 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
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 485 participants (actual)
Sponsor and investigators
- Lead sponsor
- Australian National University
- Sponsor type
- University, hospital or other
- Collaborators
- Helwan University, Clinica San Camilo, Argentina, Frederick Health, Dr Cipto Mangunkusumo General Hospital, Dr. Moewardi General Hospital, Surakarta, Indonesia, University of Sao Paulo, St James Connolly Memorial Hospital, University College Hospital Galway, Beaumont Hospital
- Responsible party
- Principal investigator, Frank van Haren, Australian National University
- Investigators
- Frank MP van Haren, MD, PhD, Study chair, Australian National University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04635241
- Sponsor's protocol ID
- INHALE-HEP meta-trial
- Acronym
- INHALE-HEP
- Status last verified
- Jan 2025
- First submitted
- 14 Nov 2020
- Last updated
- 17 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: This meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled trials and early phase studies.
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, Valle SJ, Neto AS, Schultz MJ, Laffey JG, Artigas A, Dixon B, Vilaseca AB, Barbera RA, Ismail TI, Mahrous RS, Badr M, DeNucci G, Sverdloff C, Camprubi-Rimblas M, Cosgrave DW, McNicholas B, Cody C, Curley G, Smoot TL, Staas S, Sann K, Sas C, Belani A, Hillman C, Manggala SK, Aditianingsih D, Sugiarto A, Yulianti M, Herikurniawan H, Sinto R, Auerkari AN, Permana SA, Woodcock A, Carroll M, Wilkinson T, Singh D, Shute JK, Carroll M, Page C. Efficacy of inhaled nebulised unfractionated heparin to prevent intubation or death in hospitalised patients with COVID-19: an investigator-initiated international meta-trial of randomised clinical studies. EClinicalMedicine. 2025 Sep 27;88:103339. doi: 10.1016/j.eclinm.2025.103339. eCollection 2025 Oct.
PubMed 41181828van 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 17 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- INHALEd Unfractionated HEParin for the Treatment of Hospitalised Patients With COVID-19 Meta-trial
- ClinicalTrials.gov ID
- NCT04635241
- Acronym / sponsor ID
- INHALE-HEP / INHALE-HEP meta-trial
- Conditions
- Covid19
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 485 participants (actual)
- Lead sponsor
- Australian National UniversityUniversity, hospital or other
- Collaborators
- Helwan University, Clinica San Camilo, Argentina, Frederick Health, Dr Cipto Mangunkusumo General Hospital, Dr. Moewardi General Hospital, Surakarta, Indonesia, University of Sao Paulo, St James Connolly Memorial Hospital, University College Hospital Galway, Beaumont Hospital
- Study start
- 1 Jun 2020 (actual)
- Primary completion
- 1 Nov 2023 (actual)
- Study completion
- 18 Jan 2025 (actual)
- First posted
- 19 Nov 2020 (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.
This meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled trials and early phase studies. Individual studies will be conducted in multiple countries, including Australia, the UK, the USA, Ireland, Argentina, Brazil and Egypt.
Adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, will be randomised to inhaled nebulised heparin or standard care for up to 21 days or until the patient has no respiratory symptoms. All studies will collect a minimum core dataset. The primary outcome for the meta-trial is the proportion of patients who receive invasive mechanical ventilation censored at day 28. Individual studies may have specific outcome measures in addition to the core set.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inhaled heparin | Experimental | Drug: Unfractionated heparinInhaled nebulised unfractionated heparin in addition to standard care Dose 25,000 IU every 6 hours for up to 21 days |
| Standard care | No intervention | –Standard care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients admitted to hospital with COVID-19
- No immediate requirement for mechanical ventilation (points 3-5 on the WHO ordinal scale)
- Age equal to or greater than 18
- Able to provide informed consent
Key exclusion criteria (9 listed)
- Pregnant women
- Known allergy to Heparin
- Participant in another clinical trial that is not approved for joint enrollment.
- APTT> 120 seconds, not due to anticoagulant therapy.
- Platelet count <20 x 109 per L
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 heparinInhaled nebulised 6 hourly | Drug | Inhaled heparin |
Primary outcome
Intubation rate
Time frame: Day 28
Proportion of patients requiring invasive mechanical ventilation
2 secondary outcomes
WHO ordinal scale COVID19
Time frame: Day 7
Oxygenation
Time frame: Day 7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2025.
- 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.
- Derived from this study: PubMed 41181828van Haren FMP, Valle SJ, Neto AS, Schultz MJ, Laffey JG, Artigas A, Dixon B, Vilaseca AB, Barbera RA, Ismail TI, Mahrous RS, Badr M, DeNucci G, Sverdloff C, Camprubi-Rimblas M, Cosgrave DW, McNicholas B, Cody C, Curley G, Smoot TL, Staas S, Sann K, Sas C, Belani A, Hillman C, Manggala SK, Aditianingsih D, Sugiarto A, Yulianti M, Herikurniawan H, Sinto R, Auerkari AN, Permana SA, Woodcock A, Carroll M, Wilkinson T, Singh D, Shute JK, Carroll M, Page C. Efficacy of inhaled nebulised unfractionated heparin to prevent intubation or death in hospitalised patients with COVID-19: an investigator-initiated international meta-trial of randomised clinical studies. EClinicalMedicine. 2025 Sep 27;88:103339. doi: 10.1016/j.eclinm.2025.103339. eCollection 2025 Oct.
- Derived from this study: 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: Undecided. This meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled trials and early phase studies.
Related trials for Covid19
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruiting
Intervention to Address Disparate Mental Health Consequences of COVID-19 Pandemic on Latinx and African Newcomers
Mental Health Issue, Mental Health Disorder
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
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, MD, PhD study chair
Australian National University
5 sites in 3 countries: 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 Covid19, run by Australian National University at 5 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 9 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: finished, as of the sponsor's last update on 17 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Indonesia, Argentina, Egypt. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 rate (time frame: 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 NCT04635241, which also lists 3 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 17 Jun 2025.