The Danish Pre-HCQ COVID Dialysis Study

Study Overview
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Brief Summary
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Hydroxychloroquine has been shown to inhibit replication of SARS-CoV-2 in vitro. The presented multicenter parallel-group open-label randomized clinical trial aims to investigate the efficacy of prophylactic hydroxychloroquine on mitigation of risk of hospitalization due to COVID-19 in patients with end-stage renal disease.

Detailed Description
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The emergence of a novel betacoronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic with profound implications for public health. Despite sweeping containment measures, spread of infection is ongoing, with potential ramifications pertaining to availability of health care resources. Preliminary data from Wuhan, China and Northern Italy indicate particular vulnerability of patients >60 years with pre-existing comorbidity leading to increased risk of hospitalization and death. Currently, no specific treatment has demonstrated efficacy against infection with SARS-CoV-2 in a clinical trial. However, chloroquine has been shown to inhibit both viral entry and replication in infection with SARS-CoV-2 in vitro; albeit the specific mechanisms remain unchartered. Chloroquine is an amine acidotropic form of quinine. Previously a first-choice front-line drug for the treatment and prophylaxis of malaria, chloroquine remains one of the most prescribed drugs worldwide. The possible benefit of prophylactic treatment with hydroxychloroquine for mitigation of risk of manifest SARS-COV-2 remains untested. The on-going pandemic entails particular risk for patients on chronic dialysis; chronic dialysis is both associated with profound comorbidity but also requirement of continued ambulant hospital based treatment leading to increased exposure. Consequently, the potential benefit of preventative measures is greatly increased. Aims and objectives The main objective of the following multicenter parallel-group open-label randomized clinical trial aims to investigate the possible benefit of initiating prophylactic hydroxychloroquine versus no treatment in patients on chronic dialysis for mitigation of risk related to SARS-CoV-2. The anticipated results will provide evidence as to the appropriateness of initiating prophylactic treatment for prevention of symptomatic SARS-CoV-2 in a vulnerable comorbid population with direct and immediate implications for clinical management and public health care beyond renal failure. Methods A total of 568 dialysis-treated patients with end-stage renal disease will be recruited from all dialysis centers (including satellites) in the Capital region. Patients will be randomized to either oral hydroxychloroquinesulphate 200mg once daily or no treatment for three months. The study is planned as a multicenter, open-label, parallel-group pragmatic randomized clinical study. Additionally, 100 participants on chronic in-center hemodialysis treatment will be invited to participate in a sub-study focused on SARS-CoV-2 screening and prevention. Patients will undergo screening based on oro-pharyngeal sampling twice weekly. If ≥ 20% of infected patients are identified prior to development of symptoms, results will be applied to advise early SARS-CoV-2 screening in all chronic in-center hemodialysis patients.

Official Title
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The Danish Pre-HCQ Dialysis Study: Hydroxychloroquine for Prevention of COVID19 in Dialysis-treated Patients With End-stage Renal Disease - A Multicenter Parallel-group Open Randomized Clinical Trial

Conditions
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COVID-19, End Stage Renal Disease

Intervention / Treatment
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* Drug: Hydroxychloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥18 years on chronic dialysis due to end-stage renal disease. Competence to understand the study rationale, including potential risks and benefits associated with treatment, necessary for written informed consent. Exclusion Criteria: Prior verified SARS-CoV-2 infection. Hypersensitivity reaction to chloroquine, hydroxychloroquine or 4-aminoquinolines Electrocardiogram with QTc (Bazett's formula) > 450 ms in males and 460 ms in females Patients reliant on digoxin or amiodarone treatment Pre-existing psoriasis Any pre-existing maculopathy with vision reduction Prior sensorineural hearing loss Pre-existing severe liver insufficiency (spontaneous international normalized ratio >1.5 within the last year) Pre-existing epileptic disease requiring anti-epileptic medication Pregnancy or lactation Insurmountable Language Barrier Participation in other ongoing intervention trials investigating COVID19-related outcomes

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter parallel-group open-label randomized clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hydroxychloroquine<br>Oral hydroxychloroquine 200mg once daily | Drug: Hydroxychloroquine<br>* Oral Hydroxychloroquine 200mg once daily Dose tapered if blood-hydroxychloroquine levels > 2000ng/ml<br>* Other names: Plaquenil;|
| No Intervention: No treatment<br>No treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospitalization due to SARS-CoV-2 infection | Number of patients hospitalized due to COVID-19 | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SARS-CoV-2 infection | Number of patients with verified SARS-CoV-2 infection | 3 months | 
| SARS-CoV-2 viral load | SARS-CoV-2 viral count as defined by real-time RNA polymerase chain reaction | 3 months | 
| All-cause mortality | Number of deaths within the study period | 3 months | 
| Requirement of mechanical ventilation | Number of patients requiring mechanical ventilation due to SARS-CoV-2 infection within the study period | 3 months | 
| Admission to intensive care | Number of patients admitted to intensive care due to SARS-CoV-2 infection within the study period | 3 months |