While the pandemic continues to incite panic and the guideline recommendations regardingmanagement of COVID continue to change, we have growing evidence that ARDS secondary toCovid-19 is associated with disseminated intravascular and alveolar fibrin deposition1.Strategies devised to reduce mucous and fibrin plugs will greatly help in preventingpatients from progressing to invasive ventilation2 which if happens will obviouslyoverburden the compromised intensive care facilities. Offering heparin in nebulized formhas greatly reduced levels of coagulation activation in the lungs both in animal studiesand in patients with acute lung injury3. As Heparin prevents further fibrin depositionbut is ineffective in the removal of pre-existing fibrin plug, so early use of heparinduring the course of the disease may help in limiting the complications of ARDS and hencereducing the burden faced by our intensive care units.A prospective randomized controlled trial will be carried out in patients admitted toCOVID complex to see its effects on disease progression and its role in preventingpatients from progressing to require Invasive Mechanical Ventilation while beingadministered through local route rather than systemic. Moreover, it will also giveinsight and way forward regarding the improvement in the survival and earlier discharge
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.
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
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
Pulmonology Department, Lady Reading Hospital, Peshawar
Peshawar, Khyber Pakhtunkhwa, Pakistan
Investigator: Muhammad Imran, FCPS
Contact: 03339457550
m.imran@lrh.edu.pk
Muhammad Imran, MBBS, FCPS
0092333945755
m.imran@lrh.edu.pk
Zafar Iqbal, MBBS, FCPS
00923339107037
Zafar Iqbal, FCPS, Study Chair
MTI, Lady Reading Hospital, Peshawar