Primary objective:Does addition of azithromycin to standard chloroquine treatment result in a higher clinical cure rate at day 7 than treatment with chloroquine alone in patients with COVID-19.Cure is considered when 4 criteria are present:(1) O2…
ID
Source
Brief title
Condition
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The initial response to treatment will be evaluated during admission.
Cure is considered when 4 criteria are present:
(1) O2 sat > 94% with room air
(2) 24 hours without fever (>=38°C)
(3) Breathing frequency < / = 20/min
The percentage of patients with clinical cure at day 7 will be calculated
Secondary outcome
• Does addition of azithromycin to standard chloroquine treatment result in a
higher viral clearance rate at day 7 confirmed by a negative COVID-19 PCR than
treatment with chloroquine alone in patients with COVID-19.
• Time of clinical cure (days)
• Length of stay
• Number of ICU admissions
• Mortality
• Adverse events
Other study parameters (if applicable):
- Medical history
- Comorbidities
- Smoking status
- Weight
Background summary
In early December 2019, the first pneumonia cases of unknown origin were
identified
in Wuhan, the capital city of Hubei province.(1) The pathogen has been
identified as a
novel enveloped RNA betacoronavirus (2) that has currently been named severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has a phylogenetic
similarity to SARS-CoV.(3) Patients with the infection have been documented
both in hospitals and in family settings.(4-8) The World Health Organization
(WHO) has recently
declared coronavirus disease 2019 (Covid-19) a public health emergency of
international concern. (9)
At the 27th of February the first patient has been diagnosed with COVID-19 in
the Netherlands. Since then the number of positive cases has been grown
exponentially.
The clinical features are ranging from a mild disease with upper respiratory
tract infections to severe pneumonia. Evidence based treatment recommendations
are lacking (10-15).
In the Netherlands the use of chloroquine has been recommended by the Dutch
antibiotic policy committee, because of good efficacy against SARS-COV-2
observed in vitro (SWAB, 16). In French a recent trial showed that
hydroxychloroquine treatment was significantly associated with viral load
reduction/disappearance in COVID-19 patients and its effect is reinforced by
azithromycin (17). However, this study showed some important limitations: a
randomized controlled trial had not been performed and a very small population
had been included (n=36). For these reasons we have decided to repeat the
study, but then as a randomized controlled trial and with chloroquine instead
of hydroxychloroquine. Both chloroquine and hydroxychloroquine have similar
effects in vitro against COVID-19 (16). However, there is a lack of
hydroxychloroquine medication in the Netherlands, in contrary to chloroquine.
Study objective
Primary objective:
Does addition of azithromycin to standard chloroquine treatment result in a
higher clinical cure rate at day 7 than treatment with chloroquine alone in
patients with COVID-19.
Cure is considered when 4 criteria are present:
(1) O2 sat > 94% with room air
(2) 24 hours without fever (>=38°C)
(3) Breathing frequency < / = 20/min
Study design
A prospective randomized controlled trial:
Comparing treatment of chloroquine + azithromycin with chloroquine treatment
alone for patients with PCR positive COVID-19
Intervention
One group receives chloroquine:
600 mg (6 tablets A-CQ 100 mg), 12 hours later 300 mg (3 tablets A-CQ 100 mg),
followed by 2dd 300 mg per os at day 2-5 and the other group receives
chloroquine same dosages as described before and azithromycine once daily 500
mg per os. Length of treatment: 5 days.
Study burden and risks
A number of adverse events are related with chloroquine
Retinopathy, mainly after longterm use
Skin abnormalities: pruritus, alopecia, lichen planus
QT-prolongation
Hypoglycaemia
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
• Proven diagnosis of COVID-19 by positive PCR in any specimen < 48 hours
prior to randomization.
• Age >= 18 year
• Hospitalized patients with illness of any duration, and SpO2 <= 94% on room
air
Exclusion criteria
• Severe hypoxemic respiratory failure expected to die < 72 hours after
admission
• ICU admission < 72 hours
• Allergy for chloroquine or azithromycin
• Pregnancy
• QT-prolongation: pre-existent: QTc males >450ms, QTc females > 470ms at
day 1 and at day 2
• Myasthenia gravis
• Epilepsy
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-001527-14-NL |
| CCMO | NL73610.078.20 |