Clinical trial NCT04410510: P2Et Extract in the Symptomatic Treatment of Subjects With COVID-19
Official title: Study of the P2Et Extract Obtained From Caesalpinia Spinosa in the Symptomatic Treatment of Subjects With COVID-19 at the Hospital Universitario San Ignacio, Colombia.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: COVID
Coronavirus Infection
SARS-CoV 2
COVID19
Keywords: Herbal Drug
P2Et
Caesalpinia spinosa
Coronavirus
COVID19
Lead sponsor: Hospital Universitario San Ignacio
Sponsor class: OTHER
Collaborators: name: Pontificia Universidad Javeriana
First posted: 2020-06-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized, double-blind, placebo-controlled study to demonstrate the efficacy and safety of P2Et (Caesalpinia spinosa extract) treatment in patients with a clinical diagnosis of Covid-19 infection when added to standard therapy.
Primary purpose: SUPPORTIVE_CARE

Brief summary: Antioxidants, and particularly polyphenols, have shown protection in respiratory pathologies, which is related to the decrease in the severity of the clinical picture and suppression of inflammation. This suppression of inflammation may be related to the inhibition of NF-kB polyphenols, where its activation is related to the stimulation of 150 stimuli including cytokines (IL-1β, IL-6, THF-α, GM-CSF, MCP-1), TLRs, among others. There may be other additional mechanisms that can help control virus-induced respiratory pathologies, among which are the regulation of reactive oxygen species (ROS) associated with tissue destruction caused by the virus and a selective antiviral action can be reported. direct.

The standardized P2Et extract obtained from C. spinosa, by the Immunobiology Group of the Pontificia Universidad Javeriana, is highly antioxidant, decreases lipid peroxidation and tissue damage and induces complete autophagy in stressed or tumor cells. The induction of a full autophagic flow could inhibit the replication of beta-coronaviruses like SARS-CoV-2. Furthermore, P2Et can decrease the factors involved in tissue damage by reducing IL-6 and decrease ILC2 cells of the lung in animals with lung metastases (unpublished data).

These antecedents suggest that the supplementation of patients with COVID-19 with the extract P2Et, could improve their general condition and decrease the inflammatory mediators and the viral load.

Detailed description: Phytomedicines have been used in multiple pathologies such as cancer, diabetes, HIV and respiratory pathologies, in which the inflammatory component is characterized. The extracts of these phytomedicines have a high antioxidant capacity related to the fact that their constituents are compounds of the polyphenol type, and this antioxidant mechanism has been related in part to the antiviral action they present.

Particularly, in respiratory pathologies such as SARS-CoV, MERS-CoV, and Covid-19, an important inflammatory component is observed. Patients infected with COVID-19 have high amounts of IL1-, IFN-γ, IP-10, and MCP-1, which are likely to trigger the Th1 cellular response. Furthermore, patients requiring ICU admission have higher concentrations of G-CSF, IP-10, MCP-1, MIP1-, and TNF-α, suggesting that cytokine storm is associated with the severity of the clinical picture.

Antioxidants, and particularly polyphenols, have shown protection in respiratory pathologies, which is related to the decrease in the severity of the clinical picture and suppression of inflammation. This suppression of inflammation may be related to the inhibition of NF-kB polyphenols, where its activation is related to the stimulation of 150 stimuli including cytokines (IL-1β, IL-6, THF-α, GM-CSF, MCP-1), TLRs, among others. There may be other additional mechanisms that can help control virus-induced respiratory pathologies, among which are the regulation of reactive oxygen species (ROS) associated with tissue destruction caused by the virus and a selective antiviral action can be reported direct.

The standardized P2Et extract obtained from C. spinosa, by the Immunobiology Group of the Pontificia Universidad Javeriana, is highly antioxidant, decreases lipid peroxidation and tissue damage and induces complete autophagy in stressed or tumor cells. The induction of a full autophagic flow could inhibit the replication of beta-coronaviruses like SARS-CoV-2. Furthermore, P2Et can decrease the factors involved in tissue damage by reducing IL-6 and decrease ILC2 cells of the lung in animals with lung metastases (unpublished data).

These antecedents suggest that the supplementation of patients with COVID-19 with the extract P2Et, could improve their general condition and decrease the inflammatory mediators and the viral load.

The primary outcome is to evaluate the efficacy of P2Et in reducing the length of hospital stay of patients with clinical suspicion or confirmed case of COVID-19

Eligibility criteria: Inclusion Criteria:

* Adults over 18 years old.
* Diagnosis (suspected or confirmed) of COVID-19 infection, with In-hospital management indication according to the Colombian Consensus of care, diagnosis and management of SARS-COV-2 / COVID-19 infection in health care establishments (Trujillo, 2020). Recommendations based on expert consensus and informed by evidence and the recommendations of the Ministry of Health and Social Protection for April 2020.

All patients who enter the HUSI with a clinical diagnosis of COVID-19 are eligible to enter the study if they present at least one of the following indicators of respiratory compromise:

* Hypoxemia with supplemental oxygen requirements.
* Severe pneumonia: Suspicion of respiratory infection, failure of 1 organ,
* SaO2 ambient air \<90% or respiratory rate\> 30 resp / min.
* ARDS Acute Respiratory Distress Syndrome. Clinical findings, radiographic bilateral infiltrates + oxygenation deficit: Mild: 200 mmHg \<PaO2 / FiO2 \<300 mmHg. Moderate: 100 mmHg \<PaO2 / FiO2 \<200 mmHg. Serious: PaO2 / FiO2 \<100 mmHg. If PaO2 not available SaO2 / FiO2.
* Sepsis: Defined as organic dysfunction and can be identified as an acute change in the SOFA scale\> 2 points. Quick SOFA (qSOFA) with 2 of the following 3 clinical variables can identify seriously ill patients: Glasgow 13 or lower, a systolic pressure of 100 mmHg or lower and respiratory rate of 22 / min or higher. Organic insufficiency can manifest with the following alterations: Acute confusional state, Respiratory insufficiency, Reduction in the volume of diuresis, Tachycardia, Coagulopathy, Metabolic acidosis, Lactate elevation.
* Septic shock: arterial hypotension that persists after resuscitation volume and that requires vasopressors to maintain MAP\> 65 mmHg and lactate\> 2 mmol / L (18 mg / dL) in the absence of hypovolemia.

Exclusion Criteria:

* Negative laboratory diagnostic test for COVID-19, before randomization.
* Pregnancy.
* History of allergic reactions attributed to polyphenol type compounds similar to those found in green tea.

Primary outcomes:
measure: Evaluate the efficacy of P2Et in reducing the length of hospital stay of patients with clinical suspicion or confirmed case of COVID-19
timeFrame: 30 days
Secondary outcomes:
measure: Efficacy of P2Et in reducing the time to clinically significant improvement in patients with clinical suspicion or confirmed case of COVID-19
timeFrame: 30 days
measure: Proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 14 days of treatment
timeFrame: 30 days
measure: Proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 28 days of treatment
timeFrame: 30 days
measure: Efficacy of P2Et in reducing the proportion of hospitalized patients with clinical suspicion or confirmed case of COVID-19 who require admission to the ICU due to worsening clinical symptoms.
timeFrame: 30 days
measure: Efficacy of P2Et in reducing the proportion of patients with clinical suspicion or confirmed case of COVID-19 who die from the disease.
timeFrame: 30 days
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of the P2Et in patients with COVID-19
timeFrame: 30 days
Other outcomes:
Locations:
city: Bogotá
country: Colombia
facility: Hospital Universitario San Ignacio
Study officials:
References:
citation: Uruena C, Ballesteros-Ramirez R, Gomez-Cadena A, Barreto A, Prieto K, Quijano S, Aschner P, Martinez C, Zapata-Cardona MI, El-Ahanidi H, Jandus C, Florez-Alvarez L, Rugeles MT, Zapata-Builes W, Garcia AA, Fiorentino S. Randomized double-blind clinical study in patients with COVID-19 to evaluate the safety and efficacy of a phytomedicine (P2Et). Front Med (Lausanne). 2022 Sep 8;9:991873. doi: 10.3389/fmed.2022.991873. eCollection 2022.