#StayHome: Early Hydroxychloroquine to Reduce Secondary Hospitalisation and Household Transmission in COVID-19 (#StayHome)

• ClinicalTrials.gov Identifier: NCT04385264
• Recruitment Status: Suspended
• First Posted: May 12, 2020
• Last Update Posted: May 11, 2021
• Sponsor: Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland
• Information provided by (Responsible Party): Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland

Study Description

Brief Summary:

BACKGROUND Despite drastic quarantine measures, COVID-19 continues to propagate and threatens global healthcare systems by saturating their capacity with high transmissibility and the particularly protracted length of stay needed by those requiring intensive care. Indeed, once patients advance to the ICU, prognosis is poor and it is thus critical to test medications that may prevent complications and reduce viral shedding. i.e. to protect ambulatory patients and their families from complications and transmission and allow them to #StayHome.

To date, no treatment has been reliably demonstrated as effective in COVID-19 patients.

Hydroxychloroquine (HCQ), a common and well tolerated medication, has shown promise in vitro for reducing viral replication (for SARS-CoV-2 as well as other coronaviruses with pandemic potential such as SARS-CoV-1 and MERS). Since then, several small-scale hospital-based clinical studies have indicated the potential for reduced viral shedding and hospitalisation as well as favourable evolution of lung pathology. If started earlier, this treatment could prevent complications requiring hospitalisation and intensive care, which may not be available in low-income countries.

Robust clinical trials are required to assess the potential of HCQ in COVID-19.

OBJECTIVES This trial assesses the efficacy of early treatment with HCQ in COVID-19 outpatients to reduce the incidence and severity of complications including secondary hospitalisation, ICU admissions, lung pathology and death. Secondarily, this trial will also assess its efficacy to reduce viral transmission among household contacts during self-quarantine. The clinical data collected in this trial will also be critical in creating early prognostication models to better predict healthcare needs and have evidence-based prioritization of resource allocation, which is especially critical in low-resource settings.

METHODS The trial will recruit 800 SARS-CoV-2+ patients and their household contacts at triage sites across Switzerland. Patients included are 1) at risk of poor outcome (comorbidities or >65y) and 2) well enough to self-isolate at home. These patients will be randomised 1:1 in HCQ:Placebo and given 6 days of early treatment (within 24 hours of the SARS-CoV-2 test). Intensive pragmatic multiparameter at-home follow-up (including point-of-care lung ultrasound in some sites) will continue until their outcome (resolution, or complications, such as hospitalisation, ICU admission, death). Household contacts will have before and after serological testing and social distancing knowledge and practices questionnaires to assess risk factors for infections. The household attack rate of new-onset infections can then assess the efficacy of HCQ to prevent transmission.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Hydroxychloroquine; Drug: Mannitol	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 800 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: #StayHome: Efficacy of Early Hydroxychloroquine in Outpatients to Reduce Secondary Hospitalisation and Household Transmission of COVID-19 in Switzerland: A Double-blind, Randomised, Placebo-controlled Trial
• Estimated Study Start Date: January 2022
• Estimated Primary Completion Date: August 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Placebo (Mannitol), oral capsules Day 0: 4 capsules PO OD Days 1-5: 2 capsules PO OD	Drug: Mannitol; Day 0: 4 capsules PO OD Days 1-5: 2 capsules daily PO OD; Other Name: Placebo
Experimental: Hydroxychloroquine; Hydroxychloroquine 200mg (HCQ, Plaquenil), oral capsules Day 0: 800mg PO OD (4 capsules) Days 1-5: 400mg PO OD (2 capsules daily)	Drug: Hydroxychloroquine; Day 0: 800mg PO OD (4 capsules) Days 1-5: 400mg PO OD (2 capsules daily); Other Names: Plaquenil; HCQ

Outcome Measures

Primary Outcome Measures :

1. Proportion of poor outcomes (in index cases) [ Time Frame: During the period that the subject is considered as COVID-19-positive: Average of 11 days ]
   Proportion of secondary hospitalisations (and their length), ICU admissions (and their length) and deaths.

Secondary Outcome Measures :

1. Secondary household attack rate (in household contacts) [ Time Frame: From day 0 (diagnosis and enrolment of index case) to 14 days after the outcome of the index case is recorded (recovery, hospitalisation or death): Average of 25 days ]
   Proportion of a household with new seropositivity for SARS-CoV-2
2. Subjective disease severity (in index cases) [ Time Frame: During the period that the subject is considered as COVID-19-positive: Average of 11 days ]
   An ordinal scale of disease severity using a visual analogue scale (0-10 where 0 is asymptomatic)
3. Rate of acute respiratory distress syndrome (in index cases) [ Time Frame: During the period that the subject is considered as COVID-19-positive: Average of 11 days ]
   As recorded during hospitalisation
4. Severity of radiological lung pathology (in index cases) [ Time Frame: During the period that the subject is considered as COVID-19-positive: Average of 11 days ]
   Measured with lung ultrasound, CT or x-ray
5. Objective disease severity (in index cases) [ Time Frame: During the period that the subject is considered as COVID-19-positive: Average of 11 days ]
   An ordinal scale of disease severity using the evolution of clinical biomarkers such as oxygen saturation, respiration rate etc.
6. Safety: Unintended toxic HCQ accumulation (in index cases) [ Time Frame: During the period that the subject is considered as COVID-19-positive : Average of 11 days ]
   Plasma concentrations of HCQ measured by liquid chromatography-tandem mass spectrometry
7. Safety: Adverse events (in index cases) [ Time Frame: During the period that the subject is considered as COVID-19-positive : Average of 11 days ]
   Ambulatory ECG and intensive monitoring for adverse events
8. Social distancing knowledge, attitudes and practices amongst index cases and household contacts [ Time Frame: During the period that the subject is considered as COVID-19-positive: Average of 11 days ]
   Visual analogue scores for social distancing practices (0-5, where 0 is no social distancing at all)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

INCLUSION CRITERIA (index cases):

• Age >=18 years old AND
• SARS-CoV-2 positive AND
• Well enough to self-isolate at home (at an address in Switzerland) AND

• At risk of complications from COVID-19 i.e. one or more of the following

  • Age >=65 years
  • Hypertension
  • Diabetes
  • Cardiovascular disease (History of infarction OR peripheral arteriopathy OR cerebrovascular accident OR cardiac insufficiency)
  • Chronic respiratory disease
  • Immunosuppression
  • Cancer
  • Obesity (BMI>40)

EXCLUSION CRITERIA (index cases):

• Allergy to hydroxychloroquine/4-aminoquinilones
• Retinal eye disease
• Known chronic kidney disease, stage 4 or 5 or receiving dialysis
• Weight < 40 kg
• Known porphyria
• Known psoriasis
• Known myasthenia gravis
• Taking drugs with moderate-severe interactions with HCQ
• Taking ≥ 2 QT prolonging drugs
• Taking 1 QT prolonging drug AND a loop diuretic
• Moderate or severe heart failure
• Severe or uncontrolled arrhythmia
• Recent myocardial infarction or stroke (past 6 months)
• Current pregnancy
• Current hospitalisation
• Known hemolytic anaemia

INCLUSION CRITERIA (household contacts):

• Age >1 year old AND
• Living in same household as index case during self-isolation

EXCLUSION CRITERIA (household contacts):

• History of laboratory-confirmed SARS-CoV-2 infection

Contacts and Locations

Locations

Switzerland

Unisanté

Lausanne, Vaud, Switzerland, 1015

Sponsors and Collaborators

Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland

Investigators

• Principal Investigator: Blaise Genton, MD-PhD; Unisanté
• Principal Investigator: Mary-Anne Hartley, MD, PhD MPH; Unisanté

More Information

• Responsible Party: Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland
• ClinicalTrials.gov Identifier: NCT04385264
• Other Study ID Numbers: Unisante
• First Posted: May 12, 2020
• Last Update Posted: May 11, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The aim is to share data, protocols, information sheets, CRFs and analytical code as soon as possible. Data will first be cleaned and anonymised and then subjected to rigorous assessments to secure patient privacy and analytical robustness according to the FAIR principles.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: Unknown (determined by the evolution of the epidemic)
• Access Criteria: On request by researchers agreeing to use the data for it intended purpose: i.e. to further knowledge of the efficacy and safety of HCQ in COVID-19 and to better understand the disease.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland:

Hydroxychloroquine

Additional relevant MeSH terms:

COVID-19; Coronavirus Infections; Coronaviridae Infections; Hydroxychloroquine; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Mannitol; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Diuretics, Osmotic; Diuretics; Natriuretic Agents; Physiological Effects of Drugs