LUSZ Treatment Efficacy in Hospitalized COVID-19 Patients

NCT05925140 | Recruiting Phase 1 FDA Drug

• 1 other identifier: COVID LUSZ Therapeutic
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 2

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.

Conditions

COVID-19; Hospitalized COVID-19 Patients

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Mortality rate

  The number of deaths recorded in each arm over a specified period

  28-day mortality rate

• Clinical improvement rate

  The proportion of patients showing improvement in clinical symptoms and overall health status in each arm

  28-day mortality rate

Secondary Outcomes (8)

• Time to clinical recovery

  28-day period

• Length of hospital stay

  28-day period

• Disease progression rate

  28-day period

• Adverse events

  28-day period

• Viral clearance rate

  28-day period

Study Arms (3)

LUSZ Control group: Corticosteroid Therapy-enhanced Standard Care (CTSC) alone.

ACTIVE COMPARATOR

The control group receives the standard care treatment with corticosteroid therapy.

Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)

LUSZ Antivirals Group: CTSC + Remdesivir or Lopinavir/Ritonavir.

EXPERIMENTAL

The Antivirals group receives the standard care treatment with corticosteroid therapy in combination with antiviral (Remdesivir) or antiretroviral (Lopinavir/Ritonavir) medications.

Drug: Lopinavir / Ritonavir; Drug: Remdesivir (RDV); Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)

LUSZ Immunosuppressive Group: CTSC + IL-6 receptor antagonist (Tocilizumab).

EXPERIMENTAL

The Immunosuppressive group receives the standard care treatment with corticosteroid therapy in combination with Tocilizumab, an IL-6 receptor antagonist.

Drug: Tocilizumab; Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)

Interventions

Lopinavir / Ritonavir DRUG

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.

Also known as: Kaletra

LUSZ Antivirals Group: CTSC + Remdesivir or Lopinavir/Ritonavir.

Remdesivir (RDV) DRUG

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.

Also known as: Veklury

LUSZ Antivirals Group: CTSC + Remdesivir or Lopinavir/Ritonavir.

Tocilizumab DRUG

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.

Also known as: Actemra

LUSZ Immunosuppressive Group: CTSC + IL-6 receptor antagonist (Tocilizumab).

Corticosteroid Therapy-enhanced Standard Care (CTSC) OTHER

(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

Also known as: CTSC

LUSZ Antivirals Group: CTSC + Remdesivir or Lopinavir/Ritonavir.; LUSZ Control group: Corticosteroid Therapy-enhanced Standard Care (CTSC) alone.; LUSZ Immunosuppressive Group: CTSC + IL-6 receptor antagonist (Tocilizumab).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lebanese University: lead
• Hospital Saydet Zgharta University Medical Center: collaborator

Study Sites (2)

SZUMC

Zghartā, Mohafazat Liban-Nord, Lebanon

RECRUITING

Lebanese University

Tripoli, 961, Lebanon

RECRUITING

MeSH Terms

Conditions

COVID-19; Inflammation; Disease Progression

Interventions

Lopinavir; lopinavir-ritonavir drug combination; remdesivir; tocilizumab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nehman Makdissy, Professor

  Lebanese University

  STUDY CHAIR

Central Study Contacts

Nehman Makdissy, Professor

CONTACT

+96171210250; nehman.makdissy@ul.edu.lb

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Professor

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: June 29, 2023
• Study Start: March 28, 2020
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2025
• Last Updated: February 6, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

LE (2)