Clinical trial NCT05110651: The Danish Pre-HCQ COVID Dialysis Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: COVID-19
End Stage Renal Disease
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2021-11-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter parallel-group open-label randomized clinical trial
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Hospitalization due to SARS-CoV-2 infection
timeFrame: 3 months
Secondary outcomes:
measure: SARS-CoV-2 infection
timeFrame: 3 months
measure: SARS-CoV-2 viral load
timeFrame: 3 months
measure: All-cause mortality
timeFrame: 3 months
measure: Requirement of mechanical ventilation
timeFrame: 3 months
measure: Admission to intensive care
timeFrame: 3 months
Other outcomes:
measure: Duration of hospitalization
timeFrame: 3 months
measure: Duration of mechanical ventilation
timeFrame: 3 months
measure: Duration of admission to intensive care
timeFrame: 3 months
measure: Bone marrow suppression
timeFrame: 3 months
measure: Hepatic dysfunction
timeFrame: 3 months
measure: Cardiac injury
timeFrame: 3 months
measure: Sudden cardiac death
timeFrame: 3 months
measure: QTc prolongation
timeFrame: 3 months
measure: Positiv SARS-CoV-2 antibody
timeFrame: 3 months
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Hillerød
country: Denmark
facility: North Zealand Hospital
Study officials:
affiliation: Rigshospitalet, Denmark
name: Nicholas Carlson, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: