Intranasal Heparin Treatment to Reduce Transmission Among Household Contacts of COVID 19 Positive Adults and Children

NCT ID: NCT05204550

Last Updated: 2025-04-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 506 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-30
• Study Completion Date: 2026-06-30

Brief Summary

Coronavirus-induced disease 2019 (COVID-19) is an infection caused by a virus whose full name is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This is a new and rapidly-spreading infectious disease which carries a significant risk of death, has brought massive economic impact globally and has proved hard to contain through public health measures. While we currently have effective vaccines, they do not protect the whole community and the constant threat of new mutations means there is an urgent need to identify new approaches to reducing community spread of infection.

Heparin is a naturally occurring sugar molecule which has been used for a century to treat a range of medical problems including heart attacks, strokes, and blood clots. It has also been investigated as a treatment for pneumonias. Recent research suggests it binds to the SARS-CoV-2 virus in such a way it may reduce the virus' ability to enter cells. This may be an important way to tackle the early stages of infection which occurs inside the nose. Therefore, this medication could be used amongst people with early COVID-19 infection and amongst their household contacts to reduce the rate of virus transmission during local outbreaks. If proven effective there are many other potential uses as primary prophylaxis for people working in high risk areas, for travel, for protection in high risk crowded environments such as nightclubs, or sporting events. Heparin is safe, inexpensive, available worldwide and if effective could be rapidly used across the world to slow progression of the current pandemic.

Further there are recent studies suggesting that the risk of brain complications as part of "long COVID", are directly related to the amount of virus in the nose. Reducing the viral load in the nose is thought to be effective in reducing these "long COVID" complications. This study will explore the effect of the intervention on viral load and long COVID.

In this study, researchers want to investigate this medicine in people who have been identified by a COVID-19 swab test to be in the early stages of infection(defined as the index case), and amongst their household contacts. Each participant would take the medicine or a dummy control solution by spray into their nose three times a day for 10 days. The study will investigate if there are fewer people who contract SARS-CoV-2 infection by day 10 amongst households who receive the medicine than households which receive the dummy control.

Detailed Description

Multi-centre, prospective, randomised, placebo-controlled two-arm cluster randomised superiority clinical trial.

Individual households with at least one person with Polymerase chain reaction assay(PCR) or Rapid Antigen test (RAT) confirmed SARS-CoV-2 infection will be randomised so that all consenting people in that household receive intranasal heparin or placebo.

The rate of subsequent PCR confirmed SARS-CoV-2 infections in exposed households will be measured to determine the effect of intranasal heparin on reducing transmission to close contacts.

The rate of symptom development in all participants will be used to determine effect of treatment in preventing symptomatic disease The rate of hospitalisation of all participants will be measured to determine the effect of treatment on development of severe disease.

The presence of clinical neurological long COVID symptoms will be assessed at 6 and 12 months to determine the effect of treatment on long COVID.

Objectives Primary

• To test the efficacy of early treatment and post exposure prophylaxis to reduce transmission to household contacts on SARS-CoV-2 PCR assay by day 10.

Secondary

• To test the efficacy of intranasal heparin to reduce SARS-CoV-2 viral shedding: over 10 days from day of positive swab (health professional collected nasopharyngeal swab Day 3 and 5, and Day 10: self-administered anterior nasal swab swab days 1,2,3,4,5 and 10).
• To test the safety of intranasal heparin for treatment of adult and children outpatients with SARS CoV-2 infection
• To test whether intranasal heparin administration reduces symptomatic disease in index cases and household contacts
• To test the impact of intranasal heparin on peak severity of illness.
• Quantification of replication-competent virus.
• To assess the impact of intranasal heparin on long COVID neurological symptoms

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

intranasal heparin

Unfractionated heparin (UFH) 1400u each nostril (as heparin solution 5,000u/ml, 140 microL/actuation, Two actuations each nostril) Three times daily via a plastic nasal inhalator device (APTAR, UK) for 10 days.

This is a maximal dose per day of UFH of 8400u. ie 700 x 2 actuations per nostril (1400 x2) 3 times per day (1400x2x3 = 8400u)

Group Type: EXPERIMENTAL

unfractionated heparin

Intervention Type: DRUG

intranasal

intranasal saline

Comparator 0.9% saline (as saline solution, 140 microlitres/actuation, Two actuations each nostril) Three times daily via a plastic nasal inhalator device(APTAR, UK) for 10 days.

Group Type: PLACEBO_COMPARATOR

0.9%sodium chloride

Intervention Type: DRUG

intranasal

Interventions

unfractionated heparin

intranasal

Intervention Type: DRUG

0.9%sodium chloride

intranasal

Intervention Type: DRUG

Other Intervention Names

heparin; normal saline

Eligibility Criteria

Inclusion Criteria

• Any person > 5 years of age who tests positive to SARS-CoV-2 or is a household contact of someone of any age who tests positive is eligible for the trial.
• Index case must be within 72 hours of positive test.
• The positive test can be a RAT or a standard PCR nasal swab performed at an accredited laboratory for the diagnosis of COVID-19 as per the department of health regulations. If initial test is a RAT, then a a standard PCR nasal swab performed at an accredited laboratory for the diagnosis of COVID-19 as per the department of health regulations will be collected prior to randomisation but does not delay entry into the study awaiting the confirmatory result.
• All participants must provide a signed and dated consent form and for children < 16 years have a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant's behalf. Consent forms will be developed in multiple languages and provided in a language that the participants are fluent in speaking.
• At least one other person other than the index case in each household must consent to participation to enable the consenting members of the household to be randomised. Household members who do not consent to participate in the randomised trial but whom consent to have their COVID-19 status recorded can contribute to outcome measures where relevant.

Exclusion Criteria

Children Age < 5 years are excluded from being randomised to therapy but can contribute to the outcome measures if they are swab negative on day 1.

• Documented Heparin allergy
• Previous documented heparin induced thrombocytopenia (HIT)
• Recurrent epistaxis that has required hospitalisation in last 3 months
• >72 hours since index case tested positive
• Inability to provide patient information and consent forms or study instructions in a language in which the patient is competent.
• Household members who are swab positive on day 1 are excluded from contributing to the primary outcome, but are randomised and still contribute to secondary outcomes

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Melbourne

OTHER

Sponsor Role: collaborator

Northern Hospital, Australia

OTHER

Sponsor Role: collaborator

Monash University

OTHER

Sponsor Role: collaborator

The Peter Doherty Institute for Infection and Immunity

OTHER

Sponsor Role: collaborator

St Vincent's Hospital Melbourne

OTHER

Sponsor Role: collaborator

Murdoch Childrens Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Monagle, MD

Role: PRINCIPAL_INVESTIGATOR

University of Melbourne

Donald Campbell, MD

Role: PRINCIPAL_INVESTIGATOR

Northern Hospital

Locations

The Northern Hospital

Epping, Victoria, Australia

Countries

Australia

References

Clausen TM, Sandoval DR, Spliid CB, Pihl J, Perrett HR, Painter CD, Narayanan A, Majowicz SA, Kwong EM, McVicar RN, Thacker BE, Glass CA, Yang Z, Torres JL, Golden GJ, Bartels PL, Porell RN, Garretson AF, Laubach L, Feldman J, Yin X, Pu Y, Hauser BM, Caradonna TM, Kellman BP, Martino C, Gordts PLSM, Chanda SK, Schmidt AG, Godula K, Leibel SL, Jose J, Corbett KD, Ward AB, Carlin AF, Esko JD. SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2. Cell. 2020 Nov 12;183(4):1043-1057.e15. doi: 10.1016/j.cell.2020.09.033. Epub 2020 Sep 14.

Reference Type: BACKGROUND

PMID: 32970989 (View on PubMed)

Dixon B, Smith RJ, Campbell DJ, Moran JL, Doig GS, Rechnitzer T, MacIsaac CM, Simpson N, van Haren FMP, Ghosh AN, Gupta S, Broadfield EJC, Crozier TME, French C, Santamaria JD; CHARLI Study Group. Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial. Lancet Respir Med. 2021 Apr;9(4):360-372. doi: 10.1016/S2213-2600(20)30470-7. Epub 2021 Jan 22.

Reference Type: BACKGROUND

PMID: 33493448 (View on PubMed)

van Haren FMP, Page C, Laffey JG, Artigas A, Camprubi-Rimblas M, Nunes Q, Smith R, Shute J, Carroll M, Tree J, Carroll M, Singh D, Wilkinson T, Dixon B. Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence. Crit Care. 2020 Jul 22;24(1):454. doi: 10.1186/s13054-020-03148-2.

Reference Type: BACKGROUND

PMID: 32698853 (View on PubMed)

Conzelmann C, Muller JA, Perkhofer L, Sparrer KM, Zelikin AN, Munch J, Kleger A. Inhaled and systemic heparin as a repurposed direct antiviral drug for prevention and treatment of COVID-19. Clin Med (Lond). 2020 Nov;20(6):e218-e221. doi: 10.7861/clinmed.2020-0351. Epub 2020 Aug 30.

Reference Type: BACKGROUND

PMID: 32863274 (View on PubMed)

Mycroft-West CJ, Su D, Pagani I, Rudd TR, Elli S, Gandhi NS, Guimond SE, Miller GJ, Meneghetti MCZ, Nader HB, Li Y, Nunes QM, Procter P, Mancini N, Clementi M, Bisio A, Forsyth NR, Ferro V, Turnbull JE, Guerrini M, Fernig DG, Vicenzi E, Yates EA, Lima MA, Skidmore MA. Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin. Thromb Haemost. 2020 Dec;120(12):1700-1715. doi: 10.1055/s-0040-1721319. Epub 2020 Dec 23.

Reference Type: BACKGROUND

PMID: 33368089 (View on PubMed)

Tandon R, Sharp JS, Zhang F, Pomin VH, Ashpole NM, Mitra D, McCandless MG, Jin W, Liu H, Sharma P, Linhardt RJ. Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives. J Virol. 2021 Jan 13;95(3):e01987-20. doi: 10.1128/JVI.01987-20. Print 2021 Jan 13.

Reference Type: BACKGROUND

PMID: 33173010 (View on PubMed)

Ozsoy Y, Gungor S, Cevher E. Nasal delivery of high molecular weight drugs. Molecules. 2009 Sep 23;14(9):3754-79. doi: 10.3390/molecules14093754.

Reference Type: BACKGROUND

PMID: 19783956 (View on PubMed)

Monagle K, Ryan A, Hepponstall M, Mertyn E, Monagle P, Ignjatovic V, Newall F. Inhalational use of antithrombotics in humans: Review of the literature. Thromb Res. 2015 Dec;136(6):1059-66. doi: 10.1016/j.thromres.2015.10.011. Epub 2015 Oct 9.

Reference Type: BACKGROUND

PMID: 26475409 (View on PubMed)

Figueroa JM, Lombardo ME, Dogliotti A, Flynn LP, Giugliano R, Simonelli G, Valentini R, Ramos A, Romano P, Marcote M, Michelini A, Salvado A, Sykora E, Kniz C, Kobelinsky M, Salzberg DM, Jerusalinsky D, Uchitel O. Efficacy of a Nasal Spray Containing Iota-Carrageenan in the Postexposure Prophylaxis of COVID-19 in Hospital Personnel Dedicated to Patients Care with COVID-19 Disease. Int J Gen Med. 2021 Oct 1;14:6277-6286. doi: 10.2147/IJGM.S328486. eCollection 2021.

Reference Type: BACKGROUND

PMID: 34629893 (View on PubMed)

Stelmach I, Jerzynska J, Stelmach W, Majak P, Brzozowska A, Gorski P, Kuna P. The effect of inhaled heparin on airway responsiveness to histamine and leukotriene D4. Allergy Asthma Proc. 2003 Jan-Feb;24(1):59-65.

Reference Type: BACKGROUND

PMID: 12635579 (View on PubMed)

Stelmach I, Jerzynska J, Bobrowska M, Brzozowska A, Majak P, Kuna P. [The effect of inhaled heparin on post-leukotriene bronchoconstriction in children with bronchial asthma]. Pol Merkur Lekarski. 2002 Feb;12(68):95-8. Polish.

Reference Type: BACKGROUND

PMID: 11995261 (View on PubMed)

Valencia Sanchez C, Theel E, Binnicker M, Toledano M, McKeon A. Autoimmune Encephalitis After SARS-CoV-2 Infection: Case Frequency, Findings, and Outcomes. Neurology. 2021 Dec 7;97(23):e2262-e2268. doi: 10.1212/WNL.0000000000012931. Epub 2021 Oct 11.

Reference Type: BACKGROUND

PMID: 34635560 (View on PubMed)

Misra S, Kolappa K, Prasad M, Radhakrishnan D, Thakur KT, Solomon T, Michael BD, Winkler AS, Beghi E, Guekht A, Pardo CA, Wood GK, Hsiang-Yi Chou S, Fink EL, Schmutzhard E, Kheradmand A, Hoo FK, Kumar A, Das A, Srivastava AK, Agarwal A, Dua T, Prasad K. Frequency of Neurologic Manifestations in COVID-19: A Systematic Review and Meta-analysis. Neurology. 2021 Dec 7;97(23):e2269-e2281. doi: 10.1212/WNL.0000000000012930. Epub 2021 Oct 11.

Reference Type: BACKGROUND

PMID: 34635561 (View on PubMed)

Edwards K, Corocher T, Hersusianto Y, Campbell D, Subbarao K, Neil JA, Monagle P, Ho P. Heparin-mediated PCR interference in SARS-CoV-2 assays and subsequent reversal with heparinase I. J Virol Methods. 2024 Jun;327:114944. doi: 10.1016/j.jviromet.2024.114944. Epub 2024 Apr 20.

Reference Type: DERIVED

PMID: 38649069 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

83609

Identifier Type: -

Identifier Source: org_study_id