Nebulised Heparin in Patients With COVID-19 Pneumonia

Sponsor

Lady Reading Hospital, Pakistan (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05255848

Collaborator

(none)

180

Enrollment

Location

Arms

Anticipated Duration (Months)

44.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
COVID-19 Pneumonia	Drug: Unfractionated heparin	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jun 20, 2022

Anticipated Primary Completion Date :

Aug 20, 2022

Anticipated Study Completion Date :

Oct 20, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Number of patients requiring Intubation [28 days]
The primary outcome is number of patients Invasive Mechanical Ventilation (Endotracheal Intubation)or death, for patients who died before intubation

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18 year or older.
Either gender
Currently admitted to hospital.
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
WHO Modified ordinal clinical scale 3-5

Exclusion Criteria:

Intubated and on mechanical ventilation, or requiring immediate intubation as per the treating clinician's assessment
Heparin allergy or heparin-induced thrombocytopenia
APTT >120 s, not due to anticoagulant therapy and does not correct with the administration of fresh frozen plasma
Platelet count <20 × 109 /L
Pulmonary bleeding or uncontrolled bleeding
Pregnant or might be pregnant
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 (Ceiling of care), i.e. not for intubation, not for ICU admission
Death is imminent or inevitable within 24 h
Clinician objection
Refusal to consent