Efficacy and Safety Evaluation of BZ371B in ARDS Patients

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

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

Study Overview

• Status: Terminated
• Conditions: Pulmonary Disease; ARDS; ARDS, Human
• Intervention / Treatment: Drug: Inhaled BZ371B

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 05403-900
    • InCor USP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treated Group; 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; 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.

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

Collaborators and Investigators

• Sponsor: Biozeus Biopharmaceutical S.A.
• Collaborators: InCor Heart Institute
• Investigators: Principal Investigator: Marcelo BP Amato, Phd, Department of Cardio-Pulmonar, Pulmonary Division, Hospital das Clínicas, University of São Paulo

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2022
• Primary Completion (Actual): March 3, 2023
• Study Completion (Actual): March 3, 2023

Study Registration Dates

• First Submitted: May 17, 2022
• First Submitted That Met QC Criteria: May 17, 2022
• First Posted (Actual): May 20, 2022

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: critical care; ARDS; Acute respiratory distress syndrome; Intubation; intubated; Nitric Oxide; NO; NOS; Nitric Oxide Synthase; BZ371B
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Respiratory Distress Syndrome
• Other Study ID Numbers: BZ371CLI301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No