Nalmefene improves prognosis in patients with a large cerebral infarction: study protocol and preliminary results of a randomized, controlled, prospective trial

Abstract

Background and objectives: Middle cerebral artery trunk occlusion can cause large infarctions. Clinically, thrombolytic therapy, defibrillation, vasodilation, and surgery are often used to treat these large infarctions. However, the therapeutic efficacy of these therapeutic interventions in promoting prognosis remains controversial. Nalmefene, an opioid receptor antagonist, exhibits a neuroprotective effect. Few clinical studies have reported on the therapeutic efficacy of nalmefene in the treatment of large cerebral infarctions. In this study, we investigated the therapeutic efficacy of nalmefene in restoring the neurologic function of patients with middle cerebral artery trunk infarction while using conventional treatment as a control. Design: A randomized, controlled, prospective trial. Methods: Two hundred and thirty-six patients with middle cerebral artery trunk infarction who will receive treatment at the First Hospital of Jilin University in China will be randomly divided into a control group (n = 116) and a nalmefene group (n = 120). Patients in the control group will receive conventional treatment. Patients in the nalmefene group will receive 10 successive days of intravenous nalmefene hydrochloride injection based on conventional treatment. Outcome measures and preliminary results: The primary outcome of this study is the efficacy rate at 20 days (i.e., 10 days after treatment). The secondary outcomes of this study include (1) the National Institutes of Health Stroke Scale (NIHSS) score at 20 days, which is used to evaluate neurologic function deficits; (2) Glasgow Coma Scale scores at 0 days (before treatment) and 10 days; (3) serum level of matrix metalloproteinase-9 at 0, 5, and 10 days (i.e., before treatment and 5 and 10 days of treatment); and (4) magnetic resonance imaging perfusion images of the head at 0 and 10 days. The results of a preliminary experiment involving participants receiving the same treatment as in the present study revealed that compared with the control group, the NIHSS score was significantly decreased, the efficacy rate was increased, Glasgow Coma Scale score was significantly increased, serum level of matrix metalloproteinase-9 was significantly decreased, cerebral blood flow and cerebral blood volume on the lesion side were significantly increased, and the mean transit time of contrast agent on the lesion side was significantly shortened in the nalmefene group. Discussion: Findings from this study will provide clinical evidence for use of nalmefene in combination with conventional treatment for large cerebral infarctions and data to support this combined therapy, which can improve the prognosis in patients with large cerebral infarctions. Ethics and dissemination: This study was designed in December 2011. Clinical ethics approval was received in November 2017. This trial was registered in December 2017. Patient recruitment will begin in January 2018 and end in January 2019. Data analysis will be completed in December 2019. Results will be disseminated for publication in a peer-reviewed journal. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-IOR-17013871).