A multicentric, randomized, controlled phase III study of centhaquine (Lyfaquin®) as a resuscitative agent in hypovolemic shock patients

Centhaquine is a novel, first-in-class resuscitative agent for the treatment of hypovolemic shock. Efficacy of centhaquine for the treatment of hypovolemic shock as an adjuvant to standard of care (SOC) was evaluated in a prospective, multi-center, randomized, double-blind, placebo-controlled Phase 3 study. Key inclusion criteria were; systolic blood pressure of ≤90 mm Hg, blood lactate levels of ≥2 mmol/L and patients receiving SOC in a hospital or ICU setting. Patients were randomized in a 2:1 ratio either to the centhaquine group receiving centhaquine dose of 0.01 mg/kg by IV infusion along with SOC or to the control group receiving SOC plus saline. Primary endpoints of the study were change in systolic blood pressure (SBP) and diastolic blood pressure (DBP), change in blood lactate levels and change in base deficit. Mortality through day 28 was the key secondary endpoint. A total of 197 patients were screened, of which 105 patients met the eligibility criteria and were included in the study. Out of 105 patients, 71 patients were randomized to centhaquine group and 34 patients to control group. Demographics and baseline characteristics of patients in both groups was comparable. Hemoglobin level was 9.38 ± 0.71 g/dL and 8.73 ± 0.55 g/dL in control and centhaquine groups, respectively at the time of inclusion in the study. At 24 hours of resuscitation, SBP of more than 110 mmHg was in 59.38% patients of control and 81.82% patients of centhaquine group (P=0.00842). Similarly, at 24 hours of resuscitation, DBP of more than 70 mmHg was in 50.00% patients in control group and 78.46% patients in centhaquine group (P=0.002175). The number of patients with blood lactate levels of 1.5 mmol/L or less were 46.88% in the group with standard treatment compared to 69.35% in centhaquine group (P=0.0168). The number of patients with base-deficit of less than minus 2 were 46.88% in standard treatment group compared to 68.25% in those receiving centhaquine (P=0.0217). Centhaquine treatment significantly reduced 28-day all-cause mortality. In the control group, the mortality rate was 11.76% compared to 2.94% in the centhaquine group (odds ratio: 4.4; 95% CI 0.9651 to 23.74 and P=0.037). No drug related adverse event was reported. Centhaquine (Lyfaquin®) is a highly efficacious resuscitative agent for the treatment of hypovolemic shock as an adjuvant to SOC. The study protocol (PMZ-2010/CT-3.1/2018) was approved by the Drug Controller General of India (DCGI), Ministry of Health and Family Welfare, Government of India and Institutional Ethics Committee of all the 14 Institutions.