Clinical trial NCT05184101: Inhaled Heparin for Hospitalised Patients With Coronavirus Disease 2019 (COVID-19)
Official title: INHALEd Nebulised Unfractionated HEParin for the Treatment of Hospitalised Patients With COVID-19 (INHALE-HEP) Australia
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: COVID-19
Lead sponsor: Australian National University
Sponsor class: OTHER
Collaborators: name: The George Institute
name: St George Hospital, Australia
name: St Vincent's Hospital Melbourne
name: John Hunter Hospital
name: Royal North Shore Hospital
First posted: 2022-01-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: investigator-initiated, multi-centre, randomised, open-label trial
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Intubation
timeFrame: 28 days
Secondary outcomes:
measure: Mortality
timeFrame: 60 days
measure: Oxygenation
timeFrame: 28 days
measure: Length of hospitalisation
timeFrame: 60 days
Other outcomes:
measure: Ventilator free days
timeFrame: 60 days
measure: Length of Intensive Care Unit admission
timeFrame: 60 days
measure: Incidence of bleeding
timeFrame: Day 21
Locations:
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
Study officials:
affiliation: Australian National University
name: Frank MP van Haren, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.