Inhaled Heparin for Hospitalised COVID-19 Patients (INHALE-HEP)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Covid19
• Intervention / Treatment: Drug: Unfractionated heparin

• Study Type: Interventional
• Enrollment (Actual): 485
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Frank MP van Haren, MD, PhD; Phone Number: +61467051809; Email: frank.vanharen@anu.edu.au

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • San Camilo Clinic
• Egypt
  • Cairo, Egypt
    • 15th May hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard care
Experimental: Inhaled heparin; Inhaled nebulised unfractionated heparin in addition to standard care Dose 25,000 IU every 6 hours for up to 21 days	Drug: Unfractionated heparin; Inhaled nebulised 6 hourly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intubation rate	Proportion of patients requiring invasive mechanical ventilation	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WHO ordinal scale COVID19	Number of patients showing 1 or 2 point worsening on the ordinal scale	Day 7
Oxygenation	Daily ratio of partial pressure of oxygen to FiO2 (PaO2/FiO2)	Day 7

Collaborators and Investigators

• Sponsor: Australian National University
• Collaborators: Helwan University; Coney Island Hospital, Brooklyn, NY; Galeno Desenvolvimento de Pesquisas Clínicas; Frederick Health; Clinica San Camilo, Argentina
• Investigators: Study Chair: Frank MP van Haren, MD, PhD, Australian National University

Publications and helpful links

General 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): November 1, 2023
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: November 14, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: INHALE-HEP meta-trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: This meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled trials and early phase studies.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No