Inhaled Heparin for Hospitalised Patients With Coronavirus Disease 2019 (COVID-19)

COVID-19 Clinical Trial

— INHALE-HEP  

Official title:

INHALEd Nebulised Unfractionated HEParin for the Treatment of Hospitalised Patients With COVID-19 (INHALE-HEP) Australia

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05184101
• Other study ID #: INHALE-HEP Australia Version 3
• Status: Withdrawn
• Phase: Phase 2/Phase 3
• Start date: August 2023
• Est. completion date: March 1, 2024

Study information

• Verified date: February 2024
• Source: Australian National University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 1, 2024
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• 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

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Unfractionated 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.

Locations

Country	Name	City	State
Australia	St George Hospital	Kogarah	New South Wales

Sponsors (6)

Lead Sponsor	Collaborator
Australian National University	John Hunter Hospital, Royal North Shore Hospital, St George Hospital, Australia, St Vincent's Hospital Melbourne, The George Institute

Country where clinical trial is conducted

Australia, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Ventilator free days	The number of days without invasive mechanical ventilation censored at day 60	60 days
Other	Length of Intensive Care Unit admission	Duration of intensive care unit (ICU) admission censored at day 60	60 days
Other	Incidence of bleeding	The rate of bleeding including pulmonary bleeding or other major bleeding assessed daily during intervention censored at 21 days	Day 21
Primary	Intubation	The primary outcome is intubation (or death, for patients who died before intubation) before or at day 28 after randomisation.	28 days
Secondary	Mortality	Survival to hospital discharge censored at day 60	60 days
Secondary	Oxygenation	Daily ratio of oxygen saturation by pulse oximetry (SpO2) to the fraction of inspired oxygen (FiO2): (SpO2/FiO2 ratio, highest and lowest levels)	28 days
Secondary	Length of hospitalisation	Duration of hospital length of stay censored at day 60	60 days