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Nebulised Heparin in Patients With Severe COVID-19 (CHARTER-MT)

Primary Purpose

Covid19, Respiratory Failure

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Nebulised unfractionated heparin (UFH)

About this trial

This is an interventional treatment trial for Covid19 focused on measuring COVID19; ARDS; mortality; clinical trial; metaanalysis; PRCT

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age 18 years or older
Currently in an intensive care unit (ICU) or scheduled for transfer to the ICU. During the pandemic, critically ill inpatients might be cared for outside of the walls of the usual physical environment of ICU. For this reason, ICU is defined as an area designated for inpatient care of the critically ill where therapies including invasive mechanical ventilation can be provided.
Endotracheal tube in place
Intubated yesterday or today
PaO2 to FIO2 ratio less than or equal to 300 while intubated
Acute opacities not fully explained by effusions, lobar/lung collapse and nodules, affecting at least one lung quadrant on chest X-ray or CT
The acute opacities on chest X-ray or CT are most likely due to COVID-19
There is a PCR positive sample for SARS-CoV-2 within the past 21 days or there are results pending or further testing is planned. The sample can be a nasal or pharyngeal swab, sputum, tracheal aspirate, bronchoalveolar lavage, or another sample from the patient.

Exclusion Criteria:

Enrolled in another clinical trial that is unapproved for co-enrolment
Heparin allergy or heparin-induced thrombocytopaenia (HIT)
APTT > 120 seconds and this is not due to anticoagulant therapy
Platelet count < 20 x 109 per L
Pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning
Uncontrolled bleeding
Pregnant or might be pregnant. Females aged 18-49 years are excluded unless there is documented menopause or hysterectomy or a pregnancy test was performed and is negative.
Receiving or about to commence extracorporeal membrane oxygenation (ECMO) or high frequency oscillatory ventilation (HFOV)
Myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. Guillain-Barre syndrome
Acute brain injury that may result in long-term disability
Usually receives home oxygen
Dependent on others for personal care due to physical or cognitive decline
Death is imminent or inevitable within 24 hours
The clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification
Clinician objection
Refusal of participant (person responsible) consent.

Sites / Locations

Frederick Health HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Nebulised heparin

Control group

Arm Description

Participants assigned to "nebulised UFH" will receive nebulised UFH in addition to the standard care required as determined by the treating team. Nebulised UFH (25,000 Units in 5 mL) will be administered 6-hourly via an Aerogen Solo vibrating mesh nebuliser while patients receive invasive mechanical ventilation in ICU and for a maximum of 10 days.

Participants assigned to 'standard care' will receive the standard care required as determined by the treating team and will not be treated with nebulised heparin (Australia, Ireland). Participants assigned to "placebo" will receive Nebulised 0.9% Sodium Chloride (5 mL) administered 6-hourly via an Aerogen Solo vibrating mesh nebuliser while patients receive invasive mechanical ventilation in ICU and for a maximum of 10 days (USA).

Outcomes

Primary Outcome Measures

Alive and Ventilator Free Score

Validated hierarchical composite endpoint, based on mortality and ventilator free days, which is less prone to favour a treatment with discordant effects on survival and days free of ventilation.

Secondary Outcome Measures

Full Information

NCT ID

NCT04545541

First Posted

September 5, 2020

Last Updated

January 31, 2023

Sponsor

Australian National University

1. Study Identification

Unique Protocol Identification Number

NCT04545541

Brief Title

Nebulised Heparin in Patients With Severe COVID-19

Acronym

CHARTER-MT

Official Title

Can Nebulised HepArin Reduce morTality and Time to Extubation in Patients With COVID-19 Requiring Mechanical Ventilation Meta-Trial (CHARTER-MT): Protocol for an Investigator-initiated International Meta-trial of Randomised Studies

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 1, 2020 (Actual)

Primary Completion Date

April 2024 (Anticipated)

Study Completion Date

June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Australian National University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

The Can nebulised HepArin Reduce morTality and time to Extubation in Patients with COVID-19 Requiring mechanical ventilation Meta-Trial (CHARTER-MT) is a prospective collaborative individual patient data analysis of randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries, including Australia, Ireland, the USA, and the UK. Mechanically ventilated patients with confirmed or strongly suspected SARS-CoV-2 infection, hypoxaemia and an acute pulmonary opacity in at least one lung quadrant on chest X-ray, will be randomised to nebulised heparin 25,000 Units every 6 hours or standard care (open label studies) or placebo (blinded placebo controlled studies) for up to 10 days while mechanically ventilated. All trials will collect a minimum core dataset. The primary outcome for the meta-trial is ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Individual studies may have additional outcomes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Covid19, Respiratory Failure

Keywords

COVID19; ARDS; mortality; clinical trial; metaanalysis; PRCT

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

InvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Nebulised heparin

Arm Type

Experimental

Arm Description

Arm Title

Control group

Arm Type

No Intervention

Arm Description

Intervention Type

Drug

Intervention Name(s)

Nebulised unfractionated heparin (UFH)

Intervention Description

Nebulised UFH (25,000 Units in 5 mL) will be administered 6-hourly via an Aerogen Solo vibrating mesh nebuliser while patients receive invasive mechanical ventilation in ICU and for a maximum of 10 days.

Primary Outcome Measure Information:

Title

Alive and Ventilator Free Score

Description

Validated hierarchical composite endpoint, based on mortality and ventilator free days, which is less prone to favour a treatment with discordant effects on survival and days free of ventilation.

Time Frame

Day 28

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18 years or older Currently in an intensive care unit (ICU) or scheduled for transfer to the ICU. During the pandemic, critically ill inpatients might be cared for outside of the walls of the usual physical environment of ICU. For this reason, ICU is defined as an area designated for inpatient care of the critically ill where therapies including invasive mechanical ventilation can be provided. Endotracheal tube in place Intubated yesterday or today PaO2 to FIO2 ratio less than or equal to 300 while intubated Acute opacities not fully explained by effusions, lobar/lung collapse and nodules, affecting at least one lung quadrant on chest X-ray or CT The acute opacities on chest X-ray or CT are most likely due to COVID-19 There is a PCR positive sample for SARS-CoV-2 within the past 21 days or there are results pending or further testing is planned. The sample can be a nasal or pharyngeal swab, sputum, tracheal aspirate, bronchoalveolar lavage, or another sample from the patient. Exclusion Criteria: Enrolled in another clinical trial that is unapproved for co-enrolment Heparin allergy or heparin-induced thrombocytopaenia (HIT) APTT > 120 seconds and this is not due to anticoagulant therapy Platelet count < 20 x 109 per L Pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning Uncontrolled bleeding Pregnant or might be pregnant. Females aged 18-49 years are excluded unless there is documented menopause or hysterectomy or a pregnancy test was performed and is negative. Receiving or about to commence extracorporeal membrane oxygenation (ECMO) or high frequency oscillatory ventilation (HFOV) Myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. Guillain-Barre syndrome Acute brain injury that may result in long-term disability Usually receives home oxygen Dependent on others for personal care due to physical or cognitive decline Death is imminent or inevitable within 24 hours The clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification Clinician objection Refusal of participant (person responsible) consent.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Frank MP van Haren, MD, PhD

Phone

+61467051809

fvanharen@me.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Frank MP van Haren, MD, PhD

Organizational Affiliation

Australian National University

Official's Role

Study Chair

Facility Information:

Facility Name

Frederick Health Hospital

City

Frederick

State/Province

Maryland

ZIP/Postal Code

21701

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Thomas Smoot, PharmD BCPS

Phone

240-566-3250

tsmoot@fmh.org

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The CHARTER-MT Collaborative Research Group's executive committee, with representatives from each individual country/trial, is responsible for the meta-trial's study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. Investigators from individual trials have ownership of their trial data. A memorandum of understanding and data sharing agreement between investigators will facilitate and govern the pooling and meta-analysing of de-identified individual patient data from individual trials, as well as outline authorship.

IPD Sharing Time Frame

Real-time

Citations:

PubMed Identifier

32698853

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.

Results Reference

background

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Nebulised Heparin in Patients With Severe COVID-19

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