Resuscitative Effect of Centhaquine (Lyfaquin®) in Hypovolemic Shock Patients: A Randomized, Multicentric, Controlled Trial

Abstract

Introduction: Centhaquine (Lyfaquin^®) showed significant efficacy as a resuscitative agent in animal models of haemorrhagic shock. Its safety and tolerability were confirmed in healthy human volunteers. In this study, our primary objective was to determine the safety, and the secondary objective was to assess the efficacy of centhaquine in patients with hypovolemic shock.

Methods: A prospective, multicentre, randomized phase II study was conducted in male and female patients aged 18-70 years with hypovolemic shock having systolic BP ≤ 90 mmHg. Patients were randomized in a 1:1 ratio to either the control or centhaquine group. The control group received 100 ml of normal saline infusion over 1 h, while the centhaquine group received 0.01 mg/kg of centhaquine in 100 ml normal saline infusion over 1 h. Every patient received standard of care (SOC) and was followed for 28 days.

Results: Fifty patients were included, and 45 completed the trial: 22 in the control group and 23 in the centhaquine group. The demographics of patients in both groups were comparable. No adverse event related to centhaquine was recorded in the 28-day observation period. The baseline, Injury Scoring System score, haemoglobin, and haematocrit were similar in both groups. However, 91% of the patients in the centhaquine group needed major surgery, whereas only 68% in the control group (p = 0.0526). Twenty-eight-day all-cause mortality was 0/23 in the centhaquine group and 2/22 in the control group. The percent time in ICU and ventilator support was less in the centhaquine group than in the control group. The total amount of vasopressors needed in the first 48 h of resuscitation was lower in the centhaquine group than in the control group (3.12 ± 2.18 vs. 9.39 ± 4.28 mg). An increase in systolic and diastolic BP from baseline through 48 h was more marked in the centhaquine group than in the control group. Compared with the control group, blood lactate level was lower by 1.75 ± 1.07 mmol/l in the centhaquine group on day 3 of resuscitation. Improvements in base deficit, multiple organ dysfunction syndrome (MODS) score and adult respiratory distress syndrome (ARDS) were greater in the centhaquine group than in the control group.

Conclusion: When added to SOC, centhaquine is a well-tolerated and effective resuscitative agent. It improves the clinical outcome of patients with hypovolemic shock.

Trial registration: ClinicalTrials.gov identifier number: NCT04056065.

Keywords: Centhaquine; Haemorrhage; Hypovolemia; Resuscitative agent; Shock.

Fig. 1

Patient enrolment, randomization, and trial completion

Fig. 2

Total volume of fluid, blood products, and vasopressors administered during the first 48 h in the control and centhaquine group of patients. Data presented as the mean ± standard error. Each dot represents the amount administered to each patient

Fig. 3

Systolic blood pressure during the first 48 h in the control and centhaquine groups of patients. The upper panel shows data as the mean ± standard error. The lower panel shows a change in each patient's systolic blood pressure with time. Two-way ANOVA showed a significant change in systolic blood pressure in the centhaquine (p < 0.0001) but less in the control (p = 0.0261) group during the first 12 h of resuscitation

Fig. 4

Diastolic blood pressure during the first 48 h in the control and centhaquine group of patients. The upper panel shows data as the mean ± standard error. The lower panel shows a change in each patient's diastolic blood pressure with time. Two-way ANOVA showed a significant change in diastolic blood pressure in the centhaquine (p < 0.0001) but not in the control (p = 0.1812) group during the first 12 h of resuscitation

Fig. 5

Blood lactate levels on days 1 and 3 of resuscitation in the control and centhaquine group of patients. The upper panel shows data as the mean ± standard error in the control and centhaquine groups. The lower panel shows a change in each patient's blood lactate levels on days 1 and 3 of the control (p = 0.0682) and centhaquine (p = 0.0007) groups