Official Title
Efficacy and Safety of Umifenovir as an Adjuvant Therapy Compared to the Control Therapeutic Regiment of Interferon Beta 1a, Lopinavir / Ritonavir and a Single Dose of Hydroxychloroquine in Moderate to Severe COVID-19: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial
Brief Summary

The present study is a randomized, double-blind, placebo-controlled, clinical trial, with the approval of the ethics committee will be conducted on patients who have a positive test confirming COVID-19 in Loghman Hakim Medical Education Center in Tehran. Patients will be randomly assigned to the two arms of the study and after completing the course of treatment and collecting and analyzing the necessary information from each patient, the results of the study will be published both on this site and in the form of an article in a reputable international journal.

Detailed Description

Umifenovir is a component derived from indole, which has showed positive efficacy in
inhibition of virus-to-host cell attachment in different groups of influenza, and type C
hepatitis virus. Another study in 2008 also corroborated the anti-viral effect of Arbidol on
SARS-CoV in the cell cultures. Recent works of L. Deng and other colleagues in 11th march
2020 revealed that COVID-19 patients under the treatment of Arbidol Combined with LPV/r had a
significant clinical improvement in comparison to patients administrated with LPV/r alone. A
small trial has illustrated that COVID-19 infected cases who were treated by Arbidol had an
impressive reduction in fatality rate along with a better efficacy of treatment, in
comparison with those administrated with Kaletra. Nevertheless, it is still needed to do
further research on the effectivity of Arbidol specifically in much larger populations, so
there can be a more solid conclusion ensured.

According to previous studies, IFN-β, amongst IFN-1s, has strong antiviral activity and also
has an acceptable safety profile. Based on possible therapeutic effects, We decided to lead
An Investigation into Beneficial Effects of Interferon Beta 1a, Compared to Interferon Beta
1b And The Base Therapeutic Regiment in Moderate to Severe COVID-19. In a 2003 study, SARS
was treated with different human interferons and found that IFN-β was 5 to 10 times more
effective than other types of interferons and the strongest antiviral drug possible against
SARS-CoV.

Chloroquine has been a broadly-utilized anti-malaria agent which back in 2006, had been
proved to be a powerful wide-spectrum antiviral. Moreover, Chloroquine has the
characteristics of anti-inflammatory and immune-modulatory by inhibiting the production of
TNF-α along with IL-6. In the first half of February, a study illustrated puissant inhibition
of SARS-CoV-2 by Chloroquine, when taking two 500-mg tablets of it by mouth per day; similar
to some clinical studies in China through this outbreak. According to the news briefing of a
study, it was indicated that chloroquine phosphate actually outdo the control treatment in
inhibition of pneumonia exacerbation, improving lung imaging findings, and curtailing the
disease course. Another study evaluated the possible doses of CQ and HCQ to find the
optimized dose in treatment of COVID-19. They revealed that while within in-vitro settings
Hydroxychloroquine is more potent than chloroquine. As a conclusion, they suggested a 800 mg
daily dose of hydroxychloroquine, followed by an overall maintenance dose of 400 mg per day
divided in two separate doses, which was three-fold more potent compared to the 500 mg twice
daily administration of chloroquine in 5 days. The new study published in 16th March, pointed
out that hydroxychloroquine was notably effectual in eradicating SARS-CoV-2 from the
nasopharynx. Currently the evidence is quite inconclusive about the effectiveness or
comparative effectiveness of either HCQ or CQ. Moreover, CQ has recently become scarce and
even unavailable for ordering due to a huge demand for it, all because of a significant
interest gained as a potential medicinal alternative for the management of COVID-19. In spite
of all, the primary experience in China and France is propitious for the potential role of
chloroquine, or alternatively hydroxychloroquine, for managing COVID-19.

Lopinavir, classified in the drug group of protease inhibitors, is utilized for the treatment
of patients affected prolongedly with HIV-1. The mechanism by which Lopinavir acts is
blocking the main protease of SARS-CoV-1, resulting in inhibition of viral replication.
Real-world information supporting the treatment of COVID-19 with LPV/r keep coming out.
Others have discovered that LPV/r has an anti-SARS-CoV effect within both in-vitro settings
and clinical studies. In disclosed results of Young and colleagues' research on COVID-19
patients in Singapore, 5 cases received LPV/r monotherapy. Among those 5 patients, 3 had
decrease in oxygen requirements after treatment, while the other 2 had their conditions
worsened to the point of respiratory failure. Other published evaluations from Korea and
China made up of a total of 6 patients, show reduced viral load, and clinical improvement
after onset of LPV/r treatment. Latterly, Cao and colleagues illustrated the results of
comparing twice a day use of LPV/r 400/100 mg to standard care, for treating the pneumonia
caused by SARS-CoV-2. This study's upshot, demonstrated no benefit regarding a
lopinavir-ritonavir treatment beyond standard care. Considering the currently available data,
it is yet to be determined whether LPV/r could significantly affect the status of COVID-19
patients, either as monotherapy or in combination-therapy. Moreover, close monitoring is
needed during the administration of this drug, because particularly elevated levels of AST or
ALT suggesting the gastrointestinal complications and hepatoxicity may exclude patients with
COVID-19 from clinical trials.

The present study is a randomized, double-blind, placebo-controlled, clinical trial, with the
approval of the ethics committee will be conducted on patients who have a positive test
confirming COVID-19 in Loghman Hakim Medical Education Center in Tehran. Patients will be
randomly assigned to the two arms of the study and after completing the course of treatment
and collecting and analyzing the necessary information from each patient, the results of the
study will be published both on this site and in the form of an article in a reputable
international journal.

Unknown status
COVID-19

Drug: Umifenovir

This will be drug only used in the intervention arm of our study, designed mainly to assess the additional efficacy and safety of Umifenovir in COVID-19 patients.

Drug: Interferon-β 1a

This Drug will be used in all arms as we discovered its benefits in our previous randomized clinical trial.

Drug: Lopinavir / Ritonavir

This Drug will be used in all arms as mandated by our governmental guidelines.

Drug: Single Dose of Hydroxychloroquine

This Drug will be used in all arms as mandated by our governmental guidelines.

Drug: Standards of Care

This Drug will be used in all arms as mandated by our governmental guidelines.

Eligibility Criteria

Inclusion Criteria:

- Age ≥ 18

- COVID-19 Confirmed Cases (Either RT-PCR or CT Scan Confirmed).

- Tympanic Temperature of ≥37.5 AND at least one of the following: Cough, Sputum
production, nasal discharge, myalgia, headache or fatigue) on admission.

- Time of onset of the symptoms should be acute ( Days ≤ 10).

- SpO2 ≤ 93%

- Respiratory Rate ≥ 22

Exclusion Criteria:

- Refusal to participate expressed by patient or legally authorized representative if
they are present.

- Patients with prolonged QT or PR intervals, Second or Third Degree heart block,
Arrhythmias including torsade de pointes

- Patients using drugs with potential interaction with Umifenovir Hydroxychloroquine,
Lopinavir/Ritonavir or Interferon-β 1a.

- Pregnant or lactating women.

- History of alcohol or drug addiction in the past 5 years.

- Blood ALT/AST levels > 5 times the upper limit of normal on laboratory results.

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
Iran, Islamic Republic of
Locations

Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences and Health Services
Tehran, Iran, Islamic Republic of

Shahid Beheshti University of Medical Sciences
NCT Number
Keywords
Covid-19
novel coronavirus
Umifenovir
Interferon Beta 1a
Arbidol
Lopinavir/ritonavir
Kaletra
Chloroquine
hydroxychloroquine
Interferon
MeSH Terms
COVID-19
Interferons
Ritonavir
Lopinavir
Interferon-beta
Interferon beta-1a
Hydroxychloroquine