Efficacy and Safety Evaluation of BZ371B in ARDS Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate safety, tolerability and efficacy of BZ371B in intubated patients with severe Acute Respiratory Distress Syndrome.

Detailed Description
-----------------
Acute respiratory distress syndrome (ARDS) is a severe medical condition that is triggered by an alveolar capillary membrane damage resulted from several causes. Among these causes, respiratory viral infections such as SARS-CoV-2 can be responsible for the development of the disease. ARDS presents a high mortality rate, which may range from 33-52%. The main difficulty for the treatment of this disease is dealing with hypoxia. Nitric Oxide inhalation therapy has proven to increase oxygenation and Ventilation/Perfusion by it's vasodilation property. However, there are several limitations for it's use, such as the need of a specialized equipment, systemic side effects, etc. The use of others vasodilation medications are not indicated due to their systemic systemic exposure and non-selective vasodilation. BZ371B is a small peptide that acts as a NO synthase (NOS) enhancer, inducing local NO production, and is capable to present local vasodilation effect increasing blood flow regulation, by a new and innovative mechanism of action.

Official Title
-----------------
Clinical Study to Evaluate the Efficacy and Safety od BZ371B in Patients With Acute Respiratory Distress System (ARDS) in Mechanical Ventilation, Due to Respiratory Infections

Conditions
-----------------
ARDS, ARDS, Human, Pulmonary Disease

Intervention / Treatment
-----------------
* Drug: Inhaled BZ371B


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years old or older Men or Women In Mechanical Ventilation Diagnosed with Acute Respiratory Dystress Syndrome characterized by: acute beginning (less than one week from the beggining of the disease); bilateral opacity in the Torax X-Ray (not explained by stroke, atelectasis or nodules); respiratory failure not derived from cardiac failure and water overload. P/F lower or equal to 150 mmHg with FiO2 higher or equal to 70% and PEEP higher or or equal to 88 mmHg ALready executed first pronation, followed by supine position. One hour after returning from supine position. Exclusion Criteria: Presence of pulmonary thromboembolism Presence of secondary bacterial pneumonia Severe Asthma Pregnant or lactanting women

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treated Group<br>Intubated patients treated with inhaled BZ371B will receive a dose of 12 mg of BZ371B divided in two different nebulizations per day, for three cosnecutive days | Drug: Inhaled BZ371B<br>* Intubated patients suffering from ARDS will receive BZ371B in a dose of 12 mg. This will be divided into 2 nebulizations, each with 10 ml. The first nebulization is at a dose of 3 mg and the second at a dose of 9 mg.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| P/F ratio | PaO2 divided by FiO2 measurement | 4 days | 
| Shunt ratio | Shunt ratio measurement | 4 days | 
| Ventilation-Perfusion (V/Q) ratio | V/Q measurement | 4 days | 
| Systemic blood pressure (SBP) | SBP measurement | 4 days | 
| Cardiac Function | Heart Rate (HR) and Ejection Fraction measurement | 4 days | 
| Adverse Effect | Adverse effect evaluation of compound use and application | 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary arterial pressure (PAP) | PAP measurement | 4 days | 
| Pulmonary vascular resistence | Pulmonary vascular resistance measurement | 4 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NO, ARDS, Acute respiratory distress syndrome, Intubation, intubated, critical care, Nitric Oxide, NOS, Nitric Oxide Synthase, BZ371B