The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

LUSZ Treatment Efficacy in Hospitalized COVID-19 Patients (LUSZ_AVIST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05925140
Recruitment Status : Recruiting
First Posted : June 29, 2023
Last Update Posted : February 6, 2024
Sponsor:
Collaborator:
Hospital Saydet Zgharta University Medical Center
Information provided by (Responsible Party):
Nehman Makdissy, Lebanese University

Brief Summary:
This study aims first to assess the efficacy, safety, and effectiveness of the LUSZ COVID-19 therapy consisting of a comparative study of three different treatment approaches: antiviral, antiretroviral, and immunosuppressive IL-6 receptor antagonist, and second to identify high-risk factors and biomarkers associated with fatal outcomes in hospitalized COVID-19 patients. The study seeks to validate a novel predictive scoring model for disease progression and evaluate the impact of these treatments on mortality, admission to the intensive care unit (ICU), and time to recovery.

Condition or disease Intervention/treatment Phase
COVID-19 Hospitalized COVID-19 Patients Drug: Lopinavir / Ritonavir Drug: Remdesivir (RDV) Drug: Tocilizumab Other: Corticosteroid Therapy-enhanced Standard Care (CTSC) Phase 1

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Comparative LUSZ Therapeutic Study of Antiviral, Antiretroviral, and Immunosuppressive Treatments in Hospitalized COVID-19 Patients With High-Risk Factors, Biomarkers, and Disease Progression.
Actual Study Start Date : March 28, 2020
Estimated Primary Completion Date : December 30, 2024
Estimated Study Completion Date : December 30, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Lopinavir

Arm Intervention/treatment
Active Comparator: LUSZ Control group: Corticosteroid Therapy-enhanced Standard Care (CTSC) alone.
The control group receives the standard care treatment with corticosteroid therapy.
Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)
(1) Methylprednisone (120mg/24h/IV) followed by 80mg/day (7days), and if necessary, continued with 40mg/day; or a pulse therapy (patient in critical state (360mg/day/IV) for 3 serial days, followed by 80mg/day (7days), and if necessary, continued with a dose of 40mg/day. (2) Standard Care: Normal Saline 0.9% (500cc/24h); vitamins [D (Oravil, 100.000IU/2ml PO STAT), C (10g/250cc in normal saline, 60drops/min/day), B (BECOZYME, 6 ampoules IV STAT)]; Omeprazole (RISEK, 40 mg/day IV); Paracetamol (PREFALGAN, 1g IV each 8h 3 times per day), Ketoprofen (PROFENID, 100mg/12h); Ceftriaxone (ROCEPHIN, 2g/day for 3 consecutive days), Doxycycline (VIBRAMYCIN, 100mg/12h PO for 8 days), Ivermectin (12mg/day for a period of 5 days); TOPLEXIL (Syrup, 10cc/each 8h) or SINECOD (Syrup, 15cc/each 8h); ATORVASTATIN (20mg/day); LOVENOX (40mg/12h if <80kg, or 60mg/12h if >80kg). Tranquillizers: NORMOCALM (400mg/night), XANAX (10mg/day), SEROQUEL (25mg/night), DEPIA (2mg/day), to be administered orally
Other Name: CTSC

Experimental: LUSZ Antivirals Group: CTSC + Remdesivir or Lopinavir/Ritonavir.
The Antivirals group receives the standard care treatment with corticosteroid therapy in combination with antiviral (Remdesivir) or antiretroviral (Lopinavir/Ritonavir) medications.
Drug: Lopinavir / Ritonavir

Kaletra is a medication that is produced by AbbVie, a pharmaceutical company based in the United States. It is FDA approved for the treatment of HIV-1 infection in adults and pediatric patients. Kaletra contains two active ingredients, lopinavir, and ritonavir, which work together to inhibit the replication of the HIV virus.

Administration dose and duration of treatment: Patients will receive a loading dose (800/200, daily) of lopinavir 400 mg plus ritonavir 100 mg orally every 12 h for 10 days or until discharge, if sooner.

Other Name: Kaletra

Drug: Remdesivir (RDV)

Remdesivir is provided by the United States as an FDA-approved drug, an antiviral medication developed by Gilead Sciences, and has been authorized for emergency use and approved for the treatment of COVID-19 in certain countries, including the United States.

Administration dose and duration of treatment: intravenously as a 200-mg loading dose on day 1, followed by a 100-mg once daily on days 2-10 or until hospital discharge or death. Duration is generally 5 days or until hospital discharge, whichever is first, but may extend to up to 10 days based on clinical response: For inpatients not requiring IMV and/or ECMO: 5 days; if clinical improvement is not demonstrated, treatment may be extended up to 10 days total. For inpatients requiring IMV and/or ECMO: 10 days.

Other Name: Veklury

Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)
(1) Methylprednisone (120mg/24h/IV) followed by 80mg/day (7days), and if necessary, continued with 40mg/day; or a pulse therapy (patient in critical state (360mg/day/IV) for 3 serial days, followed by 80mg/day (7days), and if necessary, continued with a dose of 40mg/day. (2) Standard Care: Normal Saline 0.9% (500cc/24h); vitamins [D (Oravil, 100.000IU/2ml PO STAT), C (10g/250cc in normal saline, 60drops/min/day), B (BECOZYME, 6 ampoules IV STAT)]; Omeprazole (RISEK, 40 mg/day IV); Paracetamol (PREFALGAN, 1g IV each 8h 3 times per day), Ketoprofen (PROFENID, 100mg/12h); Ceftriaxone (ROCEPHIN, 2g/day for 3 consecutive days), Doxycycline (VIBRAMYCIN, 100mg/12h PO for 8 days), Ivermectin (12mg/day for a period of 5 days); TOPLEXIL (Syrup, 10cc/each 8h) or SINECOD (Syrup, 15cc/each 8h); ATORVASTATIN (20mg/day); LOVENOX (40mg/12h if <80kg, or 60mg/12h if >80kg). Tranquillizers: NORMOCALM (400mg/night), XANAX (10mg/day), SEROQUEL (25mg/night), DEPIA (2mg/day), to be administered orally
Other Name: CTSC

Experimental: LUSZ Immunosuppressive Group: CTSC + IL-6 receptor antagonist (Tocilizumab).
The Immunosuppressive group receives the standard care treatment with corticosteroid therapy in combination with Tocilizumab, an IL-6 receptor antagonist.
Drug: Tocilizumab

Actemra is an FDA-approved brand name for Tocilizumab, a monoclonal antibody that targets the interleukin-6 (IL-6) receptor, an immunosuppressive drug produced by Roche. It belongs to a class of medications known as IL-6 receptor antagonists and is designed to suppress the activity of the immune system. By blocking IL-6 receptor signaling, Actemra helps reduce inflammation and is used in the treatment of various autoimmune conditions and cytokine release syndrome.

Administration dose and duration of treatment: TCZ was administered 8 mg/kg intravenously (800 mg per infusion) as a single 60-minute intravenous infusion for 4 Weeks initially. The second infusion (400 mg) after 24 h may be administered based on clinical response in case of respiratory worsening, or 8 mg/kg at T0 followed by 8 mg/kg after 12 h.

Other Name: Actemra

Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)
(1) Methylprednisone (120mg/24h/IV) followed by 80mg/day (7days), and if necessary, continued with 40mg/day; or a pulse therapy (patient in critical state (360mg/day/IV) for 3 serial days, followed by 80mg/day (7days), and if necessary, continued with a dose of 40mg/day. (2) Standard Care: Normal Saline 0.9% (500cc/24h); vitamins [D (Oravil, 100.000IU/2ml PO STAT), C (10g/250cc in normal saline, 60drops/min/day), B (BECOZYME, 6 ampoules IV STAT)]; Omeprazole (RISEK, 40 mg/day IV); Paracetamol (PREFALGAN, 1g IV each 8h 3 times per day), Ketoprofen (PROFENID, 100mg/12h); Ceftriaxone (ROCEPHIN, 2g/day for 3 consecutive days), Doxycycline (VIBRAMYCIN, 100mg/12h PO for 8 days), Ivermectin (12mg/day for a period of 5 days); TOPLEXIL (Syrup, 10cc/each 8h) or SINECOD (Syrup, 15cc/each 8h); ATORVASTATIN (20mg/day); LOVENOX (40mg/12h if <80kg, or 60mg/12h if >80kg). Tranquillizers: NORMOCALM (400mg/night), XANAX (10mg/day), SEROQUEL (25mg/night), DEPIA (2mg/day), to be administered orally
Other Name: CTSC




Primary Outcome Measures :
  1. Mortality rate [ Time Frame: 28-day mortality rate ]
    The number of deaths recorded in each arm over a specified period

  2. Clinical improvement rate [ Time Frame: 28-day mortality rate ]
    The proportion of patients showing improvement in clinical symptoms and overall health status in each arm


Secondary Outcome Measures :
  1. Time to clinical recovery [ Time Frame: 28-day period ]
    The duration taken for patients to achieve clinical recovery, such as resolution of fever, improvement in respiratory symptoms, and normalization of laboratory markers within 28-day period.

  2. Length of hospital stay [ Time Frame: 28-day period ]
    The number of days patients spend in the hospital from admission to discharge or until a predefined endpoint within a 28-day period.

  3. Disease progression rate [ Time Frame: 28-day period ]
    The rate at which patients experience disease progression, such as the development of severe respiratory distress or organ failure, within a 28-day period.

  4. Adverse events [ Time Frame: 28-day period ]
    The occurrence of any adverse events or side effects related to the treatments in each arm, including drug-related complications or complications associated with immunosuppression, within a 28-day period.

  5. Viral clearance rate [ Time Frame: 28-day period ]
    The rate at which patients in each treatment arm achieve clearance of the SARS-CoV-2 virus from respiratory samples, indicating a reduction in viral replication, within a 28-day period.

  6. Biomarker changes [ Time Frame: 28-day period ]
    Evaluation of changes in specific biomarkers associated with disease severity, inflammation, immune response, or organ dysfunction in each treatment arm within a 28-day period.

  7. Questionnaire about the quality of life [ Time Frame: 28-day period ]
    Assessment of patients' quality of life measures, including physical functioning, psychological well-being, and social aspects, using standardized questionnaires within a 28-day period.

  8. Healthcare resource utilization [ Time Frame: 28-day period ]
    Examination of the utilization of healthcare resources, such as the need for intensive care, mechanical ventilation, or other supportive interventions, in each treatment arm within a 28-day period.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Eligibility Criteria for Hospitalized Patients:

Inclusion criteria:

  • Age ≥ 18 years.
  • Gender-neutral
  • Fulfills WHO case definition, including a positive PCR for COVID-19 from any specimen (e.g., nasopharyngeal, throat, saliva, urine, stool, and other bodily fluid).
  • Not received any therapy (radiotherapy, chemotherapy, corticotherapy, hormonotherapy, immunotherapy, anti-inflammatory, antibiotics, antiparasitic, antiviral, antibacterial, convalescent plasma, monoclonal antibodies, or other treatments such as hydroxychloroquine and azithromycin) before admission and samples' collection.
  • Spo2 < 90%.
  • Moderate to severe COVID-19 cases as defined by WHO ordinal severity scale and clinical and radiological findings.
  • The time frame of symptom onset within the past 7 days.
  • Participants provide informed consent.
  • The study has received ethical approval from the institutional review board: All clinical investigations on human samples will be conducted according to the principles expressed in the Declaration of Helsinki, as revised in 2008 (http://www.wma.net/e/policy/b3.htm). All donors should provide written informed consent, and samples have to be collected in accordance with ethical codes. The study protocol was approved by the institutional review committee of the SZUMC (MA-LE-E-60/2022).

Exclusion criteria:

  • Non-SARS-CoV-2.
  • Active indication and use of one of the investigational products (e.g., HIV positive if antiretroviral agents were used).
  • Allergy or hypersensitivity to one of the investigational products (Lopinavir/Ritonavir, Remdesivir, Tocilizumab) or other contraindication.
  • Progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments.
  • Received any therapy (radiotherapy, chemotherapy, corticotherapy, hormonotherapy, immunotherapy, anti-inflammatory, antibiotics, antiparasitic, antiviral, antibacterial, convalescent plasma, monoclonal antibodies, or other treatments such as hydroxychloroquine and azithromycin) before admission and samples' collection.
  • Weight loss during the last 2 years.
  • Abdominal surgeries.
  • Pregnancy.
  • SpO2 ≥ 90%.
  • Vaccinated individuals were excluded.
  • Severe renal impairment (eGFR < 30 mL/min).
  • Liver dysfunction (Child-Pugh score ≥ 10).

All included patients should be diagnosed by polymerase chain reaction (PCR) test to be taken from a nasopharyngeal sample, throat sputum, saliva, urine, stool, or bodily fluid. Analyses are to be conducted upon admission as well as 8-10 days after admission. All patients will be followed by the principal investigator of the study. The collection of data from each patient in terms of laboratory data, treatments, and outcomes will be verified by the principal investigator through the review of clinical records. Selected patients will be divided into groups according to the WHO ordinal clinical severity scale.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05925140


Contacts
Layout table for location contacts
Contact: Nehman Makdissy, Professor +96171210250 nehman.makdissy@ul.edu.lb

Locations
Layout table for location information
Lebanon
SZUMC Recruiting
Zgharta, North, Lebanon
Contact: Fadi Fenianos, MD    +9613191528    hop.sz@hotmail.com   
Contact: Mareine Douiehy, MSc    +9613777484    hop.sz@hotmail.com   
Principal Investigator: Fadi Fenianos, MD. Infectious Diseases         
Sub-Investigator: Mareine Douiehy, MSc. Head of Quality Control         
Lebanese University Recruiting
Tripoli, Lebanon, 961
Contact: Nehman Makdissy, Professor    71210250    almakdissy@hotmail.com   
Sub-Investigator: Samar El Hamoui, PhD         
Sub-Investigator: Nadine El Ghotme, PhD         
Sub-Investigator: Wissame Daher, MSc DMAH         
Sub-Investigator: Bassam BouDeleh, MSc DMAH         
Sponsors and Collaborators
Lebanese University
Hospital Saydet Zgharta University Medical Center
Investigators
Layout table for investigator information
Study Chair: Nehman Makdissy, Professor Lebanese University
Layout table for additonal information
Responsible Party: Nehman Makdissy, Principal Investigator, Professor, Lebanese University
ClinicalTrials.gov Identifier: NCT05925140    
Other Study ID Numbers: COVID LUSZ Therapeutic
First Posted: June 29, 2023    Key Record Dates
Last Update Posted: February 6, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Nehman Makdissy, Lebanese University:
Covid-19
SARS-CoV-2
Comorbidities
Score
Inflammation
LUSZ
WHO ordinal severity scale
IL6
Antiviral
Antiretroviral
Immunosuppressive
Therapeutic treatments
Hospitalized COVID-19 patients
High-risk factors
Biomarkers
Disease Progression
Efficacy
Effectiveness
Randomized controlled trial
Treatment outcomes
Survival rates
Mortality
Safety
Additional relevant MeSH terms:
Layout table for MeSH terms
Remdesivir
COVID-19
Disease Progression
Pneumonia, Viral
Pneumonia
Respiratory Tract Infections
Infections
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Ritonavir
Lopinavir
HIV Protease Inhibitors
Viral Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antimetabolites