The Danish Pre-HCQ COVID Dialysis Study

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

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.

Study Overview

• Status: Withdrawn
• Conditions: COVID-19; End Stage Renal Disease
• Intervention / Treatment: Drug: Hydroxychloroquine

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen
    • Copenhagen, Copenhagen, Denmark, 2100
      • Rigshospitalet
  • Herlev
    • Herlev, Herlev, Denmark, 2730
      • Herlev Hospital
  • Hillerød
    • Hillerød, Hillerød, Denmark, 3400
      • North Zealand Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of hospitalization	Duration in days of hospitalization due to SARS-CoV-2 infection	3 months
Duration of mechanical ventilation	Duration in day of mechanical ventilation due to SARS-CoV-2 infection	3 months
Duration of admission to intensive care	Duration in days of admission to intensive care due to SARS-CoV-2 infection	3 months
Bone marrow suppression	Number of patients with leucopeni < 3000/μL within the study period	3 months
Hepatic dysfunction	Number of patients with hepatic dysfunction as defined by an alanine transaminaease > 250U/I within the study period	3 months
Cardiac injury	Number of patients with evidence of cardiac injury (creatinine kinase-myocardial band > 5μg/L) within the study period	3 months
Sudden cardiac death	Number of patients with sudden cardiac death within the study period	3 months
QTc prolongation	Number of patients with QTc prolongation (Bazett's formula; >> 450 ms in males and 460 ms in females)	3 months
Positiv SARS-CoV-2 antibody	Number of patients with positive SARS-CoV-2 antibody at 3 months	3 months

Collaborators and Investigators

• Sponsor: Nicholas Carlson
• Investigators: Principal Investigator: Nicholas Carlson, MD PhD, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Estimated): April 10, 2020
• Primary Completion (Actual): July 31, 2020
• Study Completion (Actual): October 1, 2020

Study Registration Dates

• First Submitted: March 29, 2020
• First Submitted That Met QC Criteria: November 5, 2021
• First Posted (Actual): November 8, 2021

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Renal Insufficiency; Renal Insufficiency, Chronic; Pathological Conditions, Signs and Symptoms; COVID-19; Kidney Failure, Chronic; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinolines; Aminoquinolines; Chloroquine; Hydroxychloroquine
• Other Study ID Numbers: D-Pre-HCQ-D104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Aggregated de-identified individual participant data for primary and secondary outcomes measures will be made available
• IPD Sharing Time Frame: Aggregated data will be available within 12 months of study completion
• IPD Sharing Access Criteria: All data access requests via email. Requestors will be required to sign a Data Access Agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• 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