Clinical trial NCT05925140: LUSZ Treatment Efficacy in Hospitalized COVID-19 Patients
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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: Lebanese University
Sponsor class: OTHER
Collaborators: name: Hospital Saydet Zgharta University Medical Center
First posted: 2023-06-29
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The ongoing COVID-19 pandemic has posed significant challenges worldwide, necessitating the evaluation of various treatment options to mitigate disease severity and improve patient outcomes. This study aims to conduct a comparative therapeutic analysis of antiviral, antiretroviral, and immunosuppressive treatments in hospitalized COVID-19 patients, named here the COVID-19 LUSZ Therapeutic Stduy. By assessing the efficacy and effectiveness of these treatment modalities, as well as considering high-risk factors, biomarkers, and disease progression, we seek to provide valuable insights into their relative benefits and inform evidence-based therapeutic strategies.

Hypothesis:

Our hypothesis is that certain antiviral, antiretroviral, and immunosuppressive treatments can effectively mitigate disease progression and improve clinical outcomes in hospitalized COVID-19 patients with different degrees of illness severity as classified by the WHO Ordinary Severity Scale (WOSS) adjusted to LUSZ scoring. We postulate that the choice of treatment may depend on the presence of high-risk factors and the underlying immune response, as reflected by biomarker profiles.

Study Design:

This study will adopt a prospective comparative design, analyzing medical records of hospitalized COVID-19 patients from multiple healthcare facilities and evaluating the disease progression. The inclusion criteria will encompass patients diagnosed with COVID-19 and receiving either antiviral, antiretroviral, or immunosuppressive treatments. Patients with comorbidities, varying levels of disease severity, and different treatment durations will be included to reflect real-world clinical scenarios.

Data Collection:

Key variables of interest will include patient demographics, medical history, disease severity at admission, laboratory results, radiology results, treatment regimen, treatment duration, and clinical outcomes. High-risk factors such as advanced age, immunocompromised status, and comorbidities will be specifically analyzed. The pulmonary inflammatory lesion, biomarkers, including inflammatory markers, cytokines, and viral load, will be assessed at various time points to evaluate treatment response and disease progression.

Analysis:

Descriptive statistics will be employed to summarize patient characteristics, treatment modalities, and clinical outcomes. Comparative analysis will be performed to assess the efficacy and effectiveness of antiviral, antiretroviral, and immunosuppressive treatments. Statistical methods, such as chi-square tests, t-tests, Kaplan-Meier survival analysis, and regression analysis, will be utilized to examine associations between treatment regimens and clinical outcomes. Subgroup analyses will be conducted to evaluate treatment response based on high-risk factors and biomarker profiles, applying the LUSZ score.

Targets and Significance:

The primary targets of this study are to compare the therapeutic effects of antiviral, antiretroviral, and immunosuppressive treatments in hospitalized COVID-19 patients and identify potential predictors of treatment response. By elucidating the relative benefits and limitations of these treatment modalities, we aim to contribute to evidence-based clinical decision-making, enhance patient care, and optimize resource allocation. Additionally, this study will provide valuable insights into the interplay between high-risk factors, biomarkers, and disease progression, which can aid in the development of personalized treatment approaches for COVID-19 patients.

In conclusion, this comparative LUSZ therapeutic study in hospitalized COVID-19 patients will provide valuable evidence regarding the efficacy and effectiveness of the LUSZ COVID-19 therapy. By considering high-risk factors, biomarkers, and disease progression, we aim to shed light on the optimal treatment strategies for different patient populations. The findings of this study have the potential to inform clinical practice, improve patient outcomes, and contribute to the ongoing efforts to combat the COVID-19 pandemic.

Eligibility 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.

Primary outcomes:
measure: Mortality rate
timeFrame: 28-day mortality rate
measure: Clinical improvement rate
timeFrame: 28-day mortality rate
Secondary outcomes:
measure: Time to clinical recovery
timeFrame: 28-day period
measure: Length of hospital stay
timeFrame: 28-day period
measure: Disease progression rate
timeFrame: 28-day period
measure: Adverse events
timeFrame: 28-day period
measure: Viral clearance rate
timeFrame: 28-day period
measure: Biomarker changes
timeFrame: 28-day period
measure: Questionnaire about the quality of life
timeFrame: 28-day period
measure: Healthcare resource utilization
timeFrame: 28-day period
Other outcomes:
Locations:
city: Zgharta
country: Lebanon
facility: SZUMC
state: North
city: Tripoli
country: Lebanon
facility: Lebanese University
Study officials:
affiliation: Lebanese University
name: Nehman Makdissy, Professor
role: STUDY_CHAIR
References: