A Randomised, Placebo-controlled Trial to Investigate the Efficacy of Intranasal Heparin Treatment to Reduce Transmission of SARS-CoV-2 Infection and COVID 19 Disease Among Household Contacts of SARS-CoV-2+ Adults and Children
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 506
- 试验地点
- 2
- 主要终点
- Number of household contacts (swab negative on day 1) testing positive for SARS-CoV-2 by PCR on either of three routine nasopharyngeal swabs on day 3,5 and 10 after enrolment or on nasopharyngeal swab in response to clinical symptoms in the first 14 days
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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
研究组 & 干预措施
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)
干预措施: unfractionated heparin (Drug)
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.
干预措施: 0.9%sodium chloride (Drug)
结局指标
主要结局
Number of household contacts (swab negative on day 1) testing positive for SARS-CoV-2 by PCR on either of three routine nasopharyngeal swabs on day 3,5 and 10 after enrolment or on nasopharyngeal swab in response to clinical symptoms in the first 14 days
时间窗: 14 days from randomisation
household contacts who become COVID 19 positive at any time during study period
次要结局
- total number of index cases and household contacts (nasopharyngeal swab positive on day 1) combined, who remain swab positive on day 3(3 days from randomisation)
- The number of participants who discontinue treatment prior to day 10 from randomisation(10 days from randomisation)
- Number of participants with clinical symptoms of neurological long COVID at 12 months post initial positive COVID-19 test.(12 months from randomisation)
- total number of index cases and household contacts (nasopharyngeal swab positive on day 1) combined, who remain swab positive on day 10(10 days from randomisation)
- Quantitative replication sub genomic viral RNA at days 3 post randomisation.(3 days from randomisation)
- Number of household contacts swab negative on day 1, hospitalized with COVID-19 by day 28 from randomization(28 days from randomisation)
- Quantitative replication sub genomic viral RNA at days 5 post randomisation.(5 days from randomisation)
- Number of index cases and household contacts swab positive on day 1, hospitalized with COVID-19 by day 28 from randomization(28 days from randomisation)
- Maximum severity score of participants (index case and household contacts swab positive on day 1 compared to household contacts swab negative on day 1) during the study period as recorded by daily symptom diary up to day 28(28 days from randomisation)
- Number of household contacts (swab negative on day 1 of study) becoming symptomatic of COVID-19 in next 28 days(28 days from randomisation)
- Quantitative replication sub genomic viral RNA at days 10 post randomisation.(10 days from randomisation)
- Number of participants with clinical symptoms of neurological long COVID at 6 months post initial positive COVID-19 test.(6 months from randomisation)
- total number of index cases and household contacts (nasopharyngeal swab positive on day 1) combined, who remain swab positive on day 5(5 days from randomisation)
- Time to swab negative based on daily anterior nasal swab for index cases and household contacts combined who were swab positive on day 1.(10 days from randomisation)
- time to symptom resolution analysis for index case and household contacts swab positive on day 1 compared to household contacts swab negative on day 1, during the study period as measured with daily symptom diary until on day 28(28 days from randomisation)