Inhaled Heparin for Hospitalised COVID-19 Patients

NCT04635241 | Completed Phase 2

• 1 other identifier: INHALE-HEP meta-trial
• Study Type: interventional
• Target: 485
• Locations: 3 countries
• Sites: 5

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• Intubation rate

  Proportion of patients requiring invasive mechanical ventilation

  Day 28

Secondary Outcomes (2)

• WHO ordinal scale COVID19

  Day 7

• Oxygenation

  Day 7

Study Arms (2)

Inhaled heparin

EXPERIMENTAL

Inhaled nebulised unfractionated heparin in addition to standard care Dose 25,000 IU every 6 hours for up to 21 days

Drug: Unfractionated heparin

Standard care

NO INTERVENTION

Standard care

Interventions

Unfractionated heparin DRUG

Inhaled nebulised 6 hourly

Inhaled heparin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• Uncontrolled bleeding
• Advanced neurological impairment
• Advanced oncological disease

Sponsors & Collaborators

• Australian National University: lead
• Helwan University: collaborator
• Clinica San Camilo, Argentina: collaborator
• Frederick Health: collaborator
• Dr Cipto Mangunkusumo General Hospital: collaborator
• Dr. Moewardi General Hospital, Surakarta, Indonesia: collaborator
• University of Sao Paulo: collaborator
• St James Connolly Memorial Hospital: collaborator
• University College Hospital Galway: collaborator
• Beaumont Hospital: collaborator

Study Sites (5)

San Camilo Clinic

Buenos Aires, Argentina

Location

15th May hospital

Cairo, Egypt

Location

RS Universitas Indonesia

Depok, Indonesia

Location

RSUP Dr Cipto Mangunkusumo

Jakarta, Indonesia

Location

RSUD Dr Moewardi

Surakarta, Indonesia

Location

Related Publications (3)

• 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.

  PMID: 32698853 BACKGROUND

• van 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.

  PMID: 41181828 DERIVED

• van 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.

  PMID: 33377218 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Heparin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Frank MP van Haren, MD, PhD

  Australian National University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 14, 2020
• First Posted: November 19, 2020
• Study Start: June 1, 2020
• Primary Completion: November 1, 2023
• Study Completion: January 18, 2025
• Last Updated: June 17, 2025

Record last verified: 2025-01

Locations

AR (1); EG (1); ID (3)