A 6-Week Prospective, Open label, Randomized, in Multicenter Study of, Oseltamivir 300mg per day plus Hydroxychloroquine 800 mg per day versus Combination of Lopipinavir 800mg (or 10 mg/kg ) per day and Ritonavir 200 mg ( or 2.5 mg/kg ) per day plus Oseltamivir 300 mg ( or 4-6 mg /kg ) per day versus Combination of Darunavir 400 mg every 8 hours plus ritonavir 200 mg (or 2.5 mg/kg ) per day plus Oseltamivir 300mg ( or 4-6 mg /kg ) per day plus Hydroxychloroquine 400 mg per day in mild COVID-19 and Combination of Lopipinavir 800 mg (or 10 mg/kg ) per day and Ritonavir 200 mg ( or 2.5 mg/kg ) per day plus Oseltamivir 300 mg ( or 4-6 mg /kg ) per day versus Favipiravir 2400 mg, 2400 mg, and 1200 mg every 8 h on day 1, and a maintenance dose of 1200 mg twice a day plus Lopipinavir 800 mg ( or 10 mg/kg ) per day and Ritonavir 200 mg ( or 2.5 mg/kg ) per day versus Combination of Darunavir 400 mg every 8 hours plus ritonavir 200 mg (or 2.5 mg/kg ) plus Oseltamivir 300 mg (or 4-6 mg /kg ) per day plus Hydroxychloroquine 400 mg per day versus Favipiravir 2400 mg, 2400 mg, and 1200 mg every 8 h on day 1, and a maintenance dose of 1200 mg twice a day plus Darunavir 400 mg every 8 hours Ritonavir 200 mg ( or 2.5 mg/kg ) per day plus Hydroxychloroquine 400 mg per day in moderate to critically illness in COVID-19
Overall Study Design and Plan Various Combination of Protease inhibitors, Oseltamivir,
Favipiravir, and Chloroquin for treatment of COVID-19. Non parametric and parametric
statistical analysis will be analysed in the efficacy of treatment. For the pair-wise
comparison, 2-sided p-value was used to ensure that the overall Type I error=0.05. Beta error
80%. Demographic and safety analyses were based on the summary of descriptive statistics.
Pre-randomization Phase The pre-randomization phase consisted of a screening period (0 to 1
day prior to randomization).
Screening Period (Day -1 to 0) At the screening visit and prior to performance of any study
procedures, the investigators would explain the details of the study and the subject would
have to sign on the written informed consent, exclusion criteria, and inclusion criteria Each
subject who was willing to enrol into the study was asked about their medical history as well
as their recent and current medications being taken. All enrolled subjects were asked to
undertake an initial physical examination and had to satisfy the criteria for the inclusion
/exclusion before being enrolled into the study.
All patients were asked to complete physical examination, CXR, CBC plt, proBNP, High
sensitive C reactive protein and Laboratory blood (livers tests, haematology,) examinations,
urine pregnancy test) were performed amount 5.5 mL for safety reasons. Nasopharyngeal swabs
were collected to detect the ORF 1ab and E genes (sensitivity: 1000 copies per milliliter) by
polymerase chain reactions. Will be performed The inclusion visit included the following
examination and tests: - physical examination,- vital signs,- weight,- CBC laboratory test
result,-Chest X ray or CT chest Blood for plasma cytokine assay -Pro BNP and High sensitive C
reactive protein, D dimer Treatment period All patient will be treated with specific arm for
10-14 days or until negative for Nasopharyngeal swabs were collected to detect the ORF 1ab
and E genes of SARS -CoV-2 for 3 consecutive tests every 24 -48 hours. ECG monitoring for
prolonged QTcB in Hydroxychloroquine arm will be closed monitored The quarantine period will
be performed for 7-14 days after swab negative All cases may be treated with Antibiotics as
prophylaxis or specific treatment Other standard treatment will be allowed for investigator
judgments. CXR nasoparyngeal swab will be performed every 1-2 days or up to investigator
judgments Follow up Visits Patient will be check up CXR and CT scan, nasoparyngeal swab will
be performed every 1-2 day until negative test and until 4-6 weeks or clinical complete
recovery.
Drug: Oral
Anti virus treatment
Inclusion Criteria:
- The subject has to grant permission to enter into the study by signing and dating the
informed consent form before completing any study-related procedure such as any
assessment or evaluation not related to the normal medical care of the subject.
- Able to give written inform consent and retained one copy of the consent form
- Male or female subject, aged between 16 - 100 years old.
- Subject diagnosed to be COVID19
- Female subject in good health and sexually active was instructed by the investigator
to avoid pregnancy during the study and to use condom or other contraceptive measure
if necessary. The subject was required to have a negative urine pregnancy test before
being eligible for the study. (At each of the subsequent visit, a urine pregnancy test
was performed).
- Subject judged to be reliable for compliance for taking medication and capable of
recording the effects of the medication and motivated in receiving benefits from the
treatment.and compliance to quarantine procedure 7-14 days after treatment
Exclusion Criteria:
- The subject was pregnant or lactating.
- The subject was a female at risk of pregnancy during the study and not taking adequate
precautions against pregnancy.
- The subject had a known hypersensitivity to any of the test materials or related
compounds.
- The subject was unable or unwilling to comply fully with the protocol.
- Treatment with investigational drug (s) within 6 months before the screening visit.
- The subject had previously entered in this study.
- Patient who planned to schedule elective surgery during the study
- The used of other antiviral agents
Assistant Professor Subsai Kongsaengdao
Bangkok, Thailand