Nebulised Heparin in Patients With COVID-19 Pneumonia

NCT05255848 | Unknown Phase 2 DMC

• 1 other identifier: 294/LRH/MTI
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

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

Conditions

COVID-19 Pneumonia

Keywords

COVID-19; Nebulised Heparin; ARDS; Intubation; Mortality

Outcome Measures

Primary Outcomes (1)

• Number of patients requiring Intubation

  The primary outcome is number of patients Invasive Mechanical Ventilation (Endotracheal Intubation)or death, for patients who died before intubation

  28 days

Secondary Outcomes (3)

• Mortality

  28 Days

• Oxygenation

  28 days

• Number of patients showing worsening or improvement on the modified WHO ordinal scale.

  Day 7

Study Arms (2)

Intervention

EXPERIMENTAL

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

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

Interventions

Unfractionated heparin DRUG

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

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lady Reading Hospital, Pakistan: lead

Study Sites (1)

Pulmonology Department, Lady Reading Hospital, Peshawar

Peshawar, Khyber Pakhtunkhwa, 25000, Pakistan

Location

Related Publications (7)

• Lio KU, Rali P. Coagulopathy in COVID-19. Lung India. 2021 Mar;38(Supplement):S53-S57. doi: 10.4103/lungindia.lungindia_226_20.

  PMID: 33686980 BACKGROUND

• 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.

  PMID: 33377218 BACKGROUND

• Imran M, Khan S, Khan S, Uddin A, Khan MS, Ambade P. COVID-19 situation in Pakistan: A broad overview. Respirology. 2021 Sep;26(9):891-892. doi: 10.1111/resp.14093. Epub 2021 May 31. No abstract available.

  PMID: 34056791 BACKGROUND

• Stilma W, Schultz MJ, Paulus F. Preventing mucus plugging in invasively ventilated intensive care unit patients-routine or personalized care and 'primum non nocere'. J Thorac Dis. 2018 Dec;10(12):E817-E818. doi: 10.21037/jtd.2018.11.128. No abstract available.

  PMID: 30746263 BACKGROUND

• Chimenti L, Camprubi-Rimblas M, Guillamat-Prats R, Gomez MN, Tijero J, Blanch L, Artigas A. Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury. Thromb Haemost. 2017 Nov;117(11):2125-2134. doi: 10.1160/TH17-05-0347. Epub 2017 Nov 30.

  PMID: 29202212 BACKGROUND

• Home - Johns Hopkins Coronavirus Resource Center. Johns Hopkins Coronavirus Resource Center 2021

  BACKGROUND

• Villar J, Blanco J, Anon JM, Santos-Bouza A, Blanch L, Ambros A, Gandia F, Carriedo D, Mosteiro F, Basaldua S, Fernandez RL, Kacmarek RM; ALIEN Network. The ALIEN study: incidence and outcome of acute respiratory distress syndrome in the era of lung protective ventilation. Intensive Care Med. 2011 Dec;37(12):1932-41. doi: 10.1007/s00134-011-2380-4. Epub 2011 Oct 14.

  PMID: 21997128 BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

Heparin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Zafar Iqbal, FCPS

  MTI, Lady Reading Hospital, Peshawar

  STUDY CHAIR

Central Study Contacts

Muhammad Imran, MBBS, FCPS

CONTACT

0092333945755; m.imran@lrh.edu.pk

Zafar Iqbal, MBBS, FCPS

CONTACT

00923339107037

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Registrar Pulmonology Unit (Principal Investigator)

Study Record Dates

• First Submitted: February 16, 2022
• First Posted: February 25, 2022
• Study Start: June 20, 2022
• Primary Completion: August 20, 2022
• Study Completion: October 20, 2022
• Last Updated: April 26, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Real-Time

Locations

PA (1)