Nebulised Heparin in Patients With COVID-19 Pneumonia

April 23, 2022 updated by: Muhammad Imran, Lady Reading Hospital, Pakistan

Role of Nebulized Heparin in Non-severe and Severe Covid-19 Patients Admitted to COVID Complex LRH, MTI: A Randomized Controlled Trial

While the pandemic continues to incite panic and the guideline recommendations regarding management of COVID continue to change, we have growing evidence that ARDS secondary to Covid-19 is associated with disseminated intravascular and alveolar fibrin deposition1. Strategies devised to reduce mucous and fibrin plugs will greatly help in preventing patients from progressing to invasive ventilation2 which if happens will obviously overburden the compromised intensive care facilities. Offering heparin in nebulized form has greatly reduced levels of coagulation activation in the lungs both in animal studies and in patients with acute lung injury3. As Heparin prevents further fibrin deposition but is ineffective in the removal of pre-existing fibrin plug, so early use of heparin during the course of the disease may help in limiting the complications of ARDS and hence reducing the burden faced by our intensive care units.

A prospective randomized controlled trial will be carried out in patients admitted to COVID complex to see its effects on disease progression and its role in preventing patients from progressing to require Invasive Mechanical Ventilation while being administered through local route rather than systemic. Moreover, it will also give insight and way forward regarding the improvement in the survival and earlier discharge

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Second-year into the deadly COVID-19 pandemic and humanity continues to get affected/infected. The world has seen a total cases of 99.7 M, a death toll of 2.14 M, and counting4. To date, Pakistan has received more than a million cases with a death count of over twenty-five thousand5. In a country like Pakistan, the burden on intensive care is substantial. So any intervention, before the patient lands in critical care units will greatly decrease the workload on the already saturated intensive care.

While the developed world has launched mass vaccination, the masses in developing countries are yet to be vaccinated. Despite the fact that vaccines have been launched in the developed world but their widespread availability in developing countries is still ambiguous6. The disease will continue to affect a larger population in the days to come so the search for new therapeutic agents must not cease. It is a fact that protective lung ventilation with low tidal volumes decreases mortality, off-label use of effective therapeutic agents that can decrease the progression to ARDS will be greatly beneficial7. There is growing evidence that ARDS secondary to Covid-19 is associated with disseminated intravascular and alveolar fibrin deposition8. Strategies to reduce mucous and fibrin plugs will greatly help patients. Nebulization of heparin may offer benefits over systemic administration because nebulization enhances delivery to the bronchial tree and the alveolar sacs and hence reduces the potential for systemic bleeding associated with intravenous administration. Moreover, heparin in nebulized form has greatly reduced levels of coagulation activation in the lungs both in animal studies and in patients with acute lung injury. As Heparin prevents further fibrin deposition but is ineffective in the removal of pre-existing fibrin plug, so early use of heparin during the course of the disease may help in limiting the complications of ARDS. Furthermore, it will also reduce the burden of patients in intensive care units. In this study, we will conduct a randomized controlled trial to see the effects of heparin in non-severe and severe COVID-19 patients to prevent progression to invasive mechanical ventilation or death.

Study Type

Interventional

Enrollment (Anticipated)

180

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Zafar Iqbal, MBBS, FCPS
  • Phone Number: 00923339107037

Study Locations

  • Pakistan
    • Khyber Pakhtunkhwa
      • Peshawar, Khyber Pakhtunkhwa, Pakistan, 25000
        • Pulmonology Department, Lady Reading Hospital, Peshawar
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 18 year or older.
  2. Either gender
  3. Currently admitted to hospital.
  4. There is a PCR-positive sample for SARS-CoV-2 within the past 21 days. The sample can be a nasal or pharyngeal swab, sputum, tracheal aspirate, Broncho alveolar lavage, or another sample from the Patient
  5. WHO Modified ordinal clinical scale 3-5

Exclusion Criteria:

  1. Intubated and on mechanical ventilation, or requiring immediate intubation as per the treating clinician's assessment
  2. Heparin allergy or heparin-induced thrombocytopenia
  3. APTT >120 s, not due to anticoagulant therapy and does not correct with the administration of fresh frozen plasma
  4. Platelet count <20 × 109 /L
  5. Pulmonary bleeding or uncontrolled bleeding
  6. Pregnant or might be pregnant
  7. Acute brain injury that may result in long-term disability
  8. Myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. Guillain-Barre syndrome
  9. Treatment limitations in place (Ceiling of care), i.e. not for intubation, not for ICU admission
  10. Death is imminent or inevitable within 24 h
  11. Clinician objection
  12. Refusal to consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention
Heparin sodium will be administered as a nebulised aerosol dose of 5000 IU heparin three times a day (TDS) via an ai compressor nebuliser plus standard of care treatment
Drug: Unfractionated heparin
Patients will be given the same standard of care treatment plus nebulized heparin 5000IU every 8 hours started 24 hours after randomization, using a compressed air nebulizer, and will be continued for one week. In case of any complication, if the attending physician feels it necessary intervention treatment will be stopped
No Intervention: No Intervention
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients requiring Intubation
Time Frame: 28 days
The primary outcome is number of patients Invasive Mechanical Ventilation (Endotracheal Intubation)or death, for patients who died before intubation
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: 28 Days
Survival to day 28 and Survival to hospital discharge, censored at day 28
28 Days
Oxygenation
Time Frame: 28 days
Daily ratio of oxygen saturation by pulse oximetry to the fraction of inspired oxygen (SpO2/FiO2 ratio, highest and lowest levels)
28 days
Number of patients showing worsening or improvement on the modified WHO ordinal scale.
Time Frame: Day 7
This is 8 points scale, starting from zero. Where 0 means uninfected and 8 means death.
Day 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lady Reading Hospital, Pakistan

Investigators

  • Study Chair: Zafar Iqbal, FCPS, MTI, Lady Reading Hospital, Peshawar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 20, 2022

Primary Completion (Anticipated)

August 20, 2022

Study Completion (Anticipated)

October 20, 2022

Study Registration Dates

First Submitted

February 16, 2022

First Submitted That Met QC Criteria

February 24, 2022

First Posted (Actual)

February 25, 2022

Study Record Updates

Last Update Posted (Actual)

April 26, 2022

Last Update Submitted That Met QC Criteria

April 23, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 294/LRH/MTI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Planned international meta-trial see NCT04635241

IPD Sharing Time Frame

Real-Time

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)
  • Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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