Nebulized Heparin for the Treatment of COVID-19 Induced Lung Injury

NCT04397510 | Terminated Phase 4 FDA Drug

• 1 other identifier: FHHep518
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized, placebo controlled study to determine if nebulized heparin may reduce the severity of lung injury caused by the novel coronavirus, also known as COVID-19

Conditions

Covid-19; ARDS, Human; Acute Lung Injury

Keywords

heparin; COVID-19; ARDS; Acute Lung Injury

Outcome Measures

Primary Outcomes (1)

• Mean daily PaO2 to FiO2 ratio

  10 days

Secondary Outcomes (4)

• Duration of mechanical ventilation

  30 days

• ICU length of stay

  30 days

• Mortality Rate

  30 days

• Incidence of adverse drug events

  10 days

Study Arms (2)

Nebulized Heparin

EXPERIMENTAL

Heparin 5,000 units/mL Dose: 25,000 units Frequency: every 6 hours Duration: 10 days

Drug: Heparin

Placebo

PLACEBO COMPARATOR

0.9% Sodium Chloride Dose: 5 mL Frequency: every 6 hours Duration: 10 days

Drug: 0.9% Sodium-chloride

Interventions

Heparin DRUG

Nebulized Heparin

Nebulized Heparin

0.9% Sodium-chloride DRUG

Nebulized 0.9% Sodium Chloride

Also known as: Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Admitted to the intensive care unit
• Positive COVID-19 PCR
• Mechanical Ventilation for ≤ 48 hours
• PaO2/FiO2 ≤300

You may not qualify if:

• Heparin allergy
• Active bleeding
• Death or withdraw of care anticipated by intensivist within 24 hours
• Platelets\< 50,000 cells/µL
• Clinically significant coagulopathy, as decided by the intensivist
• O2 dependent at baseline

Sponsors & Collaborators

• Frederick Health: lead

Study Sites (1)

Frederick Health Hospital

Frederick, Maryland, 21701, United States

Location

Related Publications (14)

• Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol. 2020 Mar;38(1):1-9. doi: 10.12932/AP-200220-0772.

  PMID: 32105090 BACKGROUND

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.

  PMID: 31986264 BACKGROUND

• Liu B, Li M, Zhou Z, Guan X, Xiang Y. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J Autoimmun. 2020 Jul;111:102452. doi: 10.1016/j.jaut.2020.102452. Epub 2020 Apr 10.

  PMID: 32291137 BACKGROUND

• Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.

  PMID: 32007143 BACKGROUND

• Mahallawi WH, Khabour OF, Zhang Q, Makhdoum HM, Suliman BA. MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile. Cytokine. 2018 Apr;104:8-13. doi: 10.1016/j.cyto.2018.01.025. Epub 2018 Feb 2.

  PMID: 29414327 BACKGROUND

• Wong CK, Lam CW, Wu AK, Ip WK, Lee NL, Chan IH, Lit LC, Hui DS, Chan MH, Chung SS, Sung JJ. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol. 2004 Apr;136(1):95-103. doi: 10.1111/j.1365-2249.2004.02415.x.

  PMID: 15030519 BACKGROUND

• Perlman S, Dandekar AA. Immunopathogenesis of coronavirus infections: implications for SARS. Nat Rev Immunol. 2005 Dec;5(12):917-27. doi: 10.1038/nri1732.

  PMID: 16322745 BACKGROUND

• Darden DB, Hawkins RB, Larson SD, Iovine NM, Prough DS, Efron PA. The Clinical Presentation and Immunology of Viral Pneumonia and Implications for Management of Coronavirus Disease 2019. Crit Care Explor. 2020 Apr 29;2(4):e0109. doi: 10.1097/CCE.0000000000000109. eCollection 2020 Apr.

  PMID: 32426751 BACKGROUND

• Camprubi-Rimblas M, Guillamat-Prats R, Lebouvier T, Bringue J, Chimenti L, Iglesias M, Obiols C, Tijero J, Blanch L, Artigas A. Role of heparin in pulmonary cell populations in an in-vitro model of acute lung injury. Respir Res. 2017 May 10;18(1):89. doi: 10.1186/s12931-017-0572-3.

  PMID: 28486961 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

• Abdelaal Ahmed Mahmoud A, Mahmoud HE, Mahran MA, Khaled M. Streptokinase Versus Unfractionated Heparin Nebulization in Patients With Severe Acute Respiratory Distress Syndrome (ARDS): A Randomized Controlled Trial With Observational Controls. J Cardiothorac Vasc Anesth. 2020 Feb;34(2):436-443. doi: 10.1053/j.jvca.2019.05.035. Epub 2019 May 27.

  PMID: 31262641 BACKGROUND

• Dixon B, Schultz MJ, Smith R, Fink JB, Santamaria JD, Campbell DJ. Nebulized heparin is associated with fewer days of mechanical ventilation in critically ill patients: a randomized controlled trial. Crit Care. 2010;14(5):R180. doi: 10.1186/cc9286. Epub 2010 Oct 11.

  PMID: 20937093 BACKGROUND

• Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

  PMID: 35244208 DERIVED

• Flumignan RL, Tinoco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD013739. doi: 10.1002/14651858.CD013739.

  PMID: 33502773 DERIVED

MeSH Terms

Conditions

COVID-19; Respiratory Distress Syndrome; Acute Lung Injury

Interventions

Heparin; Sodium Chloride

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; Respiration Disorders; Lung Injury

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Critical Care Pharmacy Specialist

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: May 21, 2020
• Study Start: June 1, 2020
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: April 3, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)