Chloroquine is one of two therapeutics (in addition to remdesivir) that has demonstrated in
vitro inhibitory effects on SARS-CoV-2 and the drug is immediately available from national
pharmacies. No delay is accordingly expected in treatment initiation after study
commencement. In light of the evidence supporting chloroquine as a promising therapeutic in
patients with COVID-19, the expected impact of the current proposal is considerable both in
the short- and long-term. If successful, treatment with chloroquine has the potential to be
the first evidence based treatment for COVID-19. The drug is affordable and the risk of side
effects is low, making it an attractive therapeutic in large proportions of the population on
a global scale.

In the current proposal aims to investigate the virological and clinical effects of
chloroquine treatment in patients with established SARS-CoV-2 in need of hospital admission.
The investigators hypothesize that early treatment with chloroquine in patients with
established COVID-19 is safe and will significantly improve prognosis and impact clinical
outcomes. More specifically, the investigators hypothesize that early treatment with
chloroquine will increase the virological clearance rate of SARS-CoV-2, and lead to more
rapid resolve of clinical symptoms, decreased proportion of patients with clinical
deterioration and a decreased admission rate to intensive care units and in-hospital
mortality. Considering the immediate and worldwide health emergency associated with the
SARS-CoV-2 outbreak and the current lack of evidence based medical interventions for this
patient group, studies investigating such possible treatment modalities in COVID-19 are
direly needed.

The study is a two-arm, open label, pragmatic randomized controlled trial (RCT) designed to
assess the virological and clinical effect of chloroquine therapy in patients with
established COVID-19. Pragmatic clinical trials are characterized by focus on informing
decision-makers on optimal clinical medicine practice and an intent to streamline procedures
and data collection in the trial. By utilizing resources already paid for by the hospitals
(physicians and nurses in daily clinical practice), pragmatic clinical trials can include a
larger number of patients at a short time duration and at a lower cost. Due to the immediate
need for study commencement and the time frame of the current proposal, a pragmatic approach
will enable swift initiation of randomization and treatment. Data will be extracted from the
data warehouse at Akershus University Hospital for eligible patient identification (i.e.
electronic surveillance) and for automatic data extraction to the study specific database.
The study will not be able to procure an acceptable placebo treatment and the study will
accordingly not be placebo-controlled.

All patients at Akershus University Hospital with suspicion of acute respiratory tract
infections are examined with a nasopharyngeal swab, with subsequent microbiological
examination, including SARS-CoV-2 specific RT-PCR. Participants will be recruited from the
entirety of the inpatients at the participating hospitals. Electronic real-time surveillance
of laboratory reports from the Department of Microbiology will be examined regularly, with
maximum interval 24 hours, for SARS-CoV-2 positive subjects.

The study aims to include patients by a sequential adaptive approach, where analyses are
planned after the inclusion of 51 patients, with subsequent analyses after 101, 151 and 202
completed patients. All patients included in each sequence will be used for the final
analyses of the entire study. This approach will enable frequent assessment of all outcome
measures.

Data will be collected from the hospital electronic record system, including electronic
patient records, laboratory and medical imaging systems, and prescribing systems. The data
warehouse at Akershus University Hospital will be utilized for automatic data extraction to
the study specific database. All clinical variables will be registered in the study eCRF
system, including clinical endpoints and quantitative virological results from serial
oropharyngeal specimens.