Re-evaluate the Efficacy and Safety of Human Urinary Kallidinogenase (RESK): Protocol for an Open-Label, Single-Arm, Multicenter Phase IV Trial for the Treatment of Acute Ischemic Stroke in Chinese Patients.

Acute ischemic stroke (AIS) is a major medical challenge in China. Thrombolytic drugs recommended for the treatment of AIS usually have a narrow time window. Human urinary kallidinogenase (HUK) was approved by the China Food and Drug Administration (CFDA) in 2005 for the treatment of mild to moderate AIS, and it is thus widely used in China. However, large-scale clinical study data for a more complete understanding of various aspects of its safety and efficacy characteristics are still unavailable. The ongoing Reevaluate the Efficacy and Safety of Human Urinary Kallidinogenase (RESK) trial is designed to reevaluate the safety and efficacy of HUK in Chinese patients with AIS. RESK is an open-label, single-arm, multicenter phase IV trial. A total of 2186 Chinese patients with AIS will be enrolled. All patients receive HUK by intravenous drip once daily for 21 consecutive days. The study has registered on ClinicalTrials.gov (NCT02562183). On 8 September 2016, 202 patients have been enrolled. Primary outcome includes the frequency and severity of adverse events. Secondary outcomes include functional improvement measured by the National Institutes of Health Stroke Scale, Barthel index, and modified Rankin Scale, and recurrence rate of ischemic stroke. Data from large-scale clinical studies are still unavailable concerning the post-marketing use of HUK. The RESK study is designed to provide a comprehensive reevaluation of the safety and efficacy of HUK in Chinese patients with AIS. TRIAL REGISTRATION: The study has registered on ClinicalTrials.gov (NCT02562183).

Urinary kallidinogenase for the treatment of cerebral arterial stenosis.

AIM: Urinary kallidinogenase (UK) has shown promise in improving cerebral perfusion. This study aimed to examine how UK affects cognitive status and serum levels of amyloid betas (Aßs) 1-40 and 1-42 in patients with cerebral arterial stenosis. METHODS: Ninety patients with cerebral arterial stenosis were enrolled, of whom 45 patients received UK + conventional treatment (UK group), and 45 patients received conventional treatment alone as control group. Cognitive status and Aß1-40 and Aß1-42 serum levels were determined before treatment and at 4 weeks and 8 weeks after treatment. RESULTS: At 4 weeks after treatment, cognitive status in patients treated with UK clearly improved accompanied by Aß1-40 serum levels decreasing while there was no change of Aß1-42. Cognitive status in patients receiving UK continued to improve, Aß1-40 serum levels declined further as well as Aß1-42 serum levels began to decrease dramatically at 8 weeks after treatment. CONCLUSION: UK could improve cognitive status and decrease both Aß1-40 and Aß1-42 serum levels to prevent ischemic cerebral injury, which represents a good option for patients with cerebral arterial stenosis.

Efficacy and safety of human urinary kallidinogenase injection for acute ischemic stroke: a systematic review.

OBJECTIVE: To assess the efficacy and safety of human urinary kallidinogenase injection (HUK) in treating patients with acute ischemic stroke. METHODS: We searched the Chinese Stroke Trials Register, the Cochrane Stroke Group Trials Register, CENTRAL, Medline, EMBASE, the China Biological Medicine Database(CBM), and the China National Knowledge Infrastructure (CNKI), which were all last searched October 2010. Randomized controlled trials (RCTs) about HUK for patients with acute ischemic stroke were included. The quality of each trial was assessed using the Cochrane Reviewers' Handbook 5.0.2. RESULTS: Twenty-four trials involving 2433 patients were included. Only two trials reported death or dependence at the end of three months follow up. In those trials, HUK reduced death or dependency comparing to the control group (relative ratio (RR) = 0.69, 95% CI 0.55 to 0.86). Twenty trials (2117 patients) reported the proportion of patients with marked neurological improvement after treatment. Meta analysis showed the HUK-treated group had more neurological improvement than did the control group (RR = 1.56, 95% CI 1.44 to 1.70). Fifteen trials reported adverse events, of which transient hypotension was most common (1.5%-5.1%). Non-fatal intracerebral hemorrhage was detected in seven patients, but the difference between the treatment and control groups was not significant (RR = 1.82, 95% CI 0.34 to 9.61). Deaths occurred in both the HUK group (0.4%) and the control group (1.1%), with no significant difference for this outcome (RR = 0.6, 95% CI 0.09 to 3.92). No trial assessed quality of life. CONCLUSIONS: Available evidence suggests that HUK injection reduces neurological impairment after acute ischemic stroke and improves long-term outcomes, though a few patients suffered from transient hypotension. Further high-quality, large scale randomized trials are needed to confirm these results.