centhaquin (PMZ2010) / Pharmazz - LARVOL DELTA

Multicentric, Randomized Study to Assess Safety and Efficacy of Centhaquine in Patients With ARDS (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Pharmazz, Inc. | N=60 ➔ 80 | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Oct 2025 ➔ Oct 2026

Enrollment change • Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

A Study to Assess Safety and Efficacy of Centhaquine as a Resuscitative Agent (clinicaltrials.gov) - P3 | N=430 | Not yet recruiting | Sponsor: Pharmazz, Inc. | Trial completion date: Oct 2025 ➔ Oct 2026 | Trial primary completion date: Oct 2025 ➔ Oct 2026

Trial completion date • Trial primary completion date

Emerging Therapeutics in Hypovolemic Shock With Centhaquine Citrate-A Novel Venopressor That Leverages the Alpha Receptor Family. (PubMed, J Cardiothorac Vasc Anesth) - No abstract available

Journal

Therapeutic Potential of Centhaquine Citrate, a Selective Alpha-2B Adrenoceptor Agonist, in the Management of Circulatory Shock. (PubMed, Drugs) - "This review outlines the sympatho-adrenergic system response after shock, discusses various vasopressors currently used as resuscitative agents, and reports the rationale for using a predominant venous vasopressor in shock. We also discuss the preliminary evidence for and ongoing research into a novel venous vasopressor, centhaquine citrate."

Journal • Review

A pilot single-centre double-blind randomised controlled trial of the effect of centhaquine on stroke volume in the treatment of vasodilatory hypotension in adults admitted to the intensive care unit (ANZCTR) - P2 | N=18 | Recruiting | Sponsor: Austin Health | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Critical care • Hypotension

Centhaquine Increases Stroke Volume and Cardiac Output in Patients with Hypovolemic Shock. (PubMed, J Clin Med) - P4 | " Centhaquine-mediated increase in venous return is critical in enhancing SV, CO, and MAP in patients with hypovolemic shock; these changes could be pivotal for reducing shock-mediated circulatory failure, promoting tissue perfusion, and improving patient outcomes. Trial Registration: CTRI/2021/01/030263 and NCT05956418."

Journal • Cardiovascular • Critical care

CENTHAQUINE: NEW HOPE! (ACC 2024) - "Timely anticipation of refractory hemorrhagic shock and use of CQ has helped these patients get a safe hemodynamic window for further evaluation and management. Systematic prospective randomized control trials are needed to find the exact role of CQ, and clearly define the appropriate stage of hemorrhagic shock when this novel drug should be used in optimal dosage."

Cardiovascular • Critical care • Dengue Fever • Hematological Disorders • Thrombocytopenia

A pilot single-centre double-blind randomised controlled trial of the effect of centhaquine on stroke volume in the treatment of vasodilatory hypotension in adults admitted to the intensive care unit (ANZCTR) - P2 | N=18 | Not yet recruiting | Sponsor: Austin Health

New P2 trial • Cardiovascular • Critical care • Hypotension

Effect of Centhaquine on the Coagulation Cascade in Normal State and Uncontrolled Hemorrhage: A Multiphase Study Combining Ex Vivo and In Vivo Experiments in Different Species. (PubMed, Int J Mol Sci) - "In normal rat blood, centhaquine did not alter R, K, α, MA, or LY30 values of the normal vehicle group or the antithrombotic effects of aspirin and heparin. In the Sal-MAP 60 group, TEG showed no change in R, an increase in α (p < 0.001), a decrease in K (p < 0.01), and a decrease in MA (p = 0.029) compared to the Centh-MAP 45 group. In conclusion, centhaquine does not impair coagulation and facilitates hemostatic resuscitation."

Journal • Preclinical • Anesthesia • Critical care • Hematological Disorders

Catalyst-free anti-Markovnikov hydroamination and hydrothiolation of vinyl heteroarenes in aqueous medium: an improved process towards centhaquine. (PubMed, Org Biomol Chem) - "The scalability of the process has been demonstrated by synthesizing centhaquine at a 19.65 g scale. A comparative analysis of the present process with previous approaches has been provided on the basis of green chemistry metrics."

Journal

Shear Stress and Endothelial Mechanotransduction in Trauma Patients with Hemorrhagic Shock: Hidden Coagulopathy Pathways and Novel Therapeutic Strategies. (PubMed, Int J Mol Sci) - "In these conditions, the cellular responses are translated into biochemical signals that induce/aggravate oxidative stress, inflammation, and coagulopathy. Microvascular shear stress-induced alterations could be treated or prevented by the development and use of innovative pharmacologic strategies that effectively target shear-mediated endothelial dysfunction, including shear-responsive drug delivery systems and novel antioxidants, and by targeting the venous side of the circulation to exploit the beneficial antithrombogenic profile of venous endothelial cells."

Journal • Review • Critical care • Hematological Disorders • Inflammation

A Study to Assess the Safety and Efficacy of Centhaquine in Hypovolemic Shock Patients (clinicaltrials.gov) - P4 | N=400 | Recruiting | Sponsor: Pharmazz, Inc.

New P4 trial

Evolutionary unmasking Resuscitative therapeutics potential of centhaquin citrate in hypovolemic shock. (PubMed, CNS Neurol Disord Drug Targets) - "Therefore, centhaquin citrate seems to be a promising entity and gaining the interest of researchers to develop it as a resuscitative agent in HS. The review gives insight into the development of centhaquin citrate as a resuscitative agent and provides insight into the associated mechanism of action and molecular signalling to foster future research on CC for its clinical use in HS."

Journal • Cardiovascular • Hematological Disorders • Inflammation

Multicentric, Randomized Study to Assess Safety and Efficacy of Centhaquine in COVID-19 Patients With ARDS (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Pharmazz, Inc. | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Oct 2024 ➔ Oct 2025

Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

A Study to Assess Safety and Efficacy of Centhaquine as a Resuscitative Agent (clinicaltrials.gov) - P3 | N=430 | Not yet recruiting | Sponsor: Pharmazz, Inc. | Trial completion date: May 2025 ➔ Oct 2025 | Trial primary completion date: Apr 2025 ➔ Oct 2025

Trial completion date • Trial primary completion date

Controls of Central and Peripheral Blood Pressure and Hemorrhagic/Hypovolemic Shock. (PubMed, J Clin Med) - "Therefore, understanding blood pressure in normal and disease conditions is essential for managing shock-related cardiovascular implications and improving treatment outcomes. In this review, we have described the control systems (neural, hormonal, osmotic, and cellular) of blood pressure and their regulation in hemorrhagic/hypovolemic shock using centhaquine (Lyfaquin) as a resuscitative agent."

Journal • Review • Cardiovascular • Hematological Disorders • Hypertension • Hypotension

Role of adrenergic receptors in shock. (PubMed, Front Physiol) - "Our group has demonstrated that a dose of .02 mg/kg body wt of centhaquine (CQ) specifically activates α2B ARs on venous circulation along with the central α2A ARs after hypovolemic/hemorrhagic shock...Thus, we have demonstrated that α2 ARs could be suitable targets for treating or managing hypovolemic/hemorrhagic shock. Further understanding of ARs in shock would help find new potential pharmacological targets."

Journal • Review • Cardiovascular • Hematological Disorders

A Study to Assess Safety and Efficacy of Centhaquine as a Resuscitative Agent (clinicaltrials.gov) - P3 | N=430 | Not yet recruiting | Sponsor: Pharmazz, Inc. | Trial completion date: Jan 2025 ➔ May 2025 | Initiation date: Dec 2022 ➔ Apr 2023 | Trial primary completion date: Dec 2024 ➔ Apr 2025

Trial completion date • Trial initiation date • Trial primary completion date

Multicentric, Randomized Study to Assess Safety and Efficacy of Centhaquine in COVID-19 Patients With ARDS (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Pharmazz, Inc. | Trial completion date: Dec 2023 ➔ Dec 2024 | Initiation date: Oct 2022 ➔ Mar 2023 | Trial primary completion date: Oct 2023 ➔ Oct 2024

Trial completion date • Trial initiation date • Trial primary completion date • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

A Study to Assess Safety and Efficacy of Centhaquine as a Resuscitative Agent (clinicaltrials.gov) - P3 | N=430 | Not yet recruiting | Sponsor: Pharmazz, Inc. | Initiation date: Sep 2022 ➔ Dec 2022 | Trial primary completion date: Sep 2024 ➔ Dec 2024

Trial initiation date • Trial primary completion date

Multicentric, Randomized Study to Assess Safety and Efficacy of Centhaquine in COVID-19 Patients With ARDS (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Pharmazz, Inc. | Trial completion date: May 2023 ➔ Dec 2023 | Initiation date: May 2022 ➔ Oct 2022 | Trial primary completion date: May 2023 ➔ Oct 2023

Trial completion date • Trial initiation date • Trial primary completion date • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

A Study to Assess Safety and Efficacy of Centhaquine as a Resuscitative Agent (clinicaltrials.gov) - P3 | N=430 | Not yet recruiting | Sponsor: Pharmazz, Inc. | Trial completion date: Sep 2024 ➔ Dec 2024 | Initiation date: Jun 2022 ➔ Sep 2022 | Trial primary completion date: Jun 2024 ➔ Sep 2024

Trial completion date • Trial initiation date • Trial primary completion date

A Study to Assess Safety and Efficacy of Centhaquine as a Resuscitative Agent (clinicaltrials.gov) - P3 | N=430 | Not yet recruiting | Sponsor: Pharmazz, Inc. | Initiation date: Mar 2022 ➔ Jun 2022 | Trial primary completion date: Mar 2024 ➔ Jun 2024

Trial initiation date • Trial primary completion date

Multicentric, Randomized Study to Assess Safety and Efficacy of Centhaquine in COVID-19 Patients With ARDS (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Pharmazz, Inc.

New P2 trial • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

A Phase-III Study to Assess Safety and Efficacy of Centhaquine as a Resuscitative Agent (clinicaltrials.gov) - P3 | N=430 | Not yet recruiting | Sponsor: Pharmazz, Inc.

New P3 trial