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.