Background: Centhaquine is a resuscitative agent that acts on alpha-2B adrenergic receptors to enhance venous return in hypovolemic shock. The effect of centhaquine on cardiac output in patients with hypovolemic shock has not been reported. Methods: Trans-thoracic echocardiography was utilized to measure stroke volume (SV), cardiac output (CO), left ventricular outflow tract-velocity time integral (LVOT-VTI), left ventricular outflow tract diameter (LVOTd), heart rate (HR), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (FS) and inferior vena cava (IVC) diameter before (0 min) and after centhaquine (0.01 mg/kg, iv infusion over 60 min) treatment (60 min, 120 min, and 300 min) in 12 randomly selected patients with hypovolemic shock enrolled in a prospective, multicenter, open-label phase IV clinical study (NCT05956418) of centhaquine in patients with hypovolemic shock. Results: A significant increase in SV (mL) was observed after 60, 120, and 300 minutes of centhaquine treatment. CO (mL/min) increased significantly at 120 and 300 min despite a decrease in HR at these times. A significant increase in IVC diameter and LVOT-VTI (mL) at these time points was observed, which indicated increased venous return. The LVEF and FS did not change, while the mean arterial pressure (MAP, mmHg) increased in patients after 120 and 300 minutes of centhaquine treatment. Positive correlations between IVC diameter and SV (R2 = 0.9556) and between IVC diameter and MAP (R2 = 0.8928) were observed, which indicated the effect of centhaquine mediated increase in venous return on SV, CO, and MAP. Conclusions: Centhaquine mediated increase in venous return appears to play a critical role 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: The phase IV trial reported in this study has Clinical Trials Registry, India; ctri.icmr.org.in, CTRI/2021/01/030263; clinicaltrials.gov, NCT05956418.

D.S. is an employee of Pharmazz India Pvt. Ltd., INDIA, and A.K.R. is an employee of Pharmazz, Inc., Willowbrook, IL, USA. A.G. is an employee of Pharmazz, Inc., Willowbrook, IL, USA, and has issued and pending patents related to this study. All the other authors declare no competing interests.

NCT05956418

Pharmazz India Pvt Ltd. supported the study.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics Approval and Consent to Participate: The study was conducted in compliance with the Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline for Good Clinical Practice (ICH-GCP), the Helsinki Declaration, and local regulatory requirements. The study protocol (PMZ-2010/CT-4.1/2019), version 1.0/ dated October 16, 2019, was approved by the Drugs Controller General of India (DCGI), Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India (DCGI CT NOC. No.: CT/ND/110/2020). Besides, each institutional ethics committee reviewed and approved the study protocol before initiating patient enrolment. The trial was registered at the Clinical Trials Registry, India (CTRI/2021/01/030263), and the United States National Library of Medicine, ClinicalTrials.gov (NCT05956418). Each site's ethics committee was informed of any protocol deviation, amendment, subject exclusion or withdrawal, and serious adverse events (SAE).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The anonymized patient datasets generated and/or analyzed during the study are available from the corresponding author on a reasonable request from a bona fide researcher/research group.