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COVID-19Phase 4UAIICNCT04350684

Umifenovir in Hospitalized COVID-19 Patients

A Phase 4 study testing Umifenovir, Interferon-β 1a and Lopinavir / Ritonavir in people with COVID-19, run by Shahid Beheshti University of Medical Sciences at 1 site in Iran.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
COVID-19
What is being tested?
Umifenovir, Interferon-β 1a and Lopinavir / Ritonavir
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteIran
Study dates
15 Apr 2020to 24 Apr 2020
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Iran1 site
  • Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences and Health Services

    Tehran

Other trials in Iran

About this study

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

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.

Read the 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.

Conditions
COVID-19
Being tested
Umifenovir, Interferon-β 1a, Lopinavir / Ritonavir, Single Dose of Hydroxychloroquine, Standards of Care
Keywords
COVID-19, Novel Coronavirus, Umifenovir, Interferon Beta 1a, Arbidol, Lopinavir/Ritonavir, Kaletra, Chloroquine, Hydroxychloroquine, Interferon
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • UmifenovirDrug

    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.

  • Interferon-β 1aDrug

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

  • Lopinavir / RitonavirDrug

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

  • Single Dose of HydroxychloroquineDrug

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

  • Standards of CareDrug

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

Study groups in NCT04350684
Study groupRoleWhat they receive
UmifenovirExperimentalUmifenovir + Interferon-β 1a + Lopinavir / Ritonavir + Single Dose of Hydroxychloroquine + Standards of Care
Receives: Drug: Umifenovir; Drug: Interferon-β 1a; Drug: Lopinavir / Ritonavir; Drug: Single Dose of Hydroxychloroquine; Drug: Standards of Care
ControlActive comparatorInterferon-β 1a + Lopinavir / Ritonavir + Single Dose of Hydroxychloroquine + Standards of Care
Receives: Drug: Interferon-β 1a; Drug: Lopinavir / Ritonavir; Drug: Single Dose of Hydroxychloroquine; Drug: Standards of Care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to clinical improvement

    Improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R\&D. Geneva: World Health Organization) or discharge from the hospital, whichever came first.

    Measured: From date of randomization until 14 days later.

Secondary outcomes (5)
  1. Mortality

    If the patient dies, we have reached an outcome.

    Measured: From date of randomization until 14 days later.

  2. SpO2 Improvement

    Pulse-oxymetry

    Measured: Days 1, 2, 3, 4, 5, 6, 7 and 14.

  3. Incidence of new mechanical ventilation use

    Incidence of new mechanical ventilation use

    Measured: From date of randomization until 14 days later.

  4. Duration of hospitalization

    Duration of hospitalization (days)

    Measured: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 14 days.

  5. Cumulative incidence of serious adverse events

    With incidence of any serious adverse effects, the outcome has happened.

    Measured: Days 1, 2, 3, 4, 5, 6, 7 and 14.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2020
  2. Study start15 Apr 2020 (estimated)
  3. Primary completion22 Apr 2020 (estimated)
  4. Study completion24 Apr 2020 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04350684
Sponsor's protocol ID
Umifenovir in COVID-19
Acronym
UAIIC
Status last verified
Apr 2020
First submitted
14 Apr 2020
Last updated
20 Apr 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: There is no further information.

Publications

  • Alavi Darazam I, Shokouhi S, Mardani M, Pourhoseingholi MA, Rabiei MM, Hatami F, Shabani M, Moradi O, Gharehbagh FJ, Irvani SSN, Amirdosara M, Hajiesmaeili M, Rezaei O, Khoshkar A, Lotfollahi L, Gachkar L, Dehbsneh HS, Khalili N, Soleymaninia A, Kusha AH, Shoushtari MT, Torabinavid P. Umifenovir in hospitalized moderate to severe COVID-19 patients: A randomized clinical trial. Int Immunopharmacol. 2021 Oct;99:107969. doi: 10.1016/j.intimp.2021.107969. Epub 2021 Jul 10.

    PubMed 34273635

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Umifenovir, Interferon-β 1a and Lopinavir / Ritonavir in people with COVID-19, run by Shahid Beheshti University of Medical Sciences at 1 site in Iran.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 20 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to clinical improvement (time frame: From date of randomization until 14 days later.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04350684, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2020.

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