Pioglitazone in spontaneous subarachnoid hemorrhage: study protocol of a multicenter, double-blind, randomized trial (PSSH)

Junhui Chen; Mingchang Li; Lei Chen; Qinyi Xu; Tengfeng Yan; Chunlei Zhang; Ping Hu; Jianqing He; Xun Zhu; Xingen Zhu; Yuhai Wang

doi:10.3389/fphar.2023.1323292

Pioglitazone in spontaneous subarachnoid hemorrhage: study protocol of a multicenter, double-blind, randomized trial (PSSH)

Front Pharmacol. 2024 Jan 5:14:1323292. doi: 10.3389/fphar.2023.1323292. eCollection 2023.

Authors

Junhui Chen^#^{1

2

3}, Mingchang Li^#², Lei Chen^#^{1

4}, Qinyi Xu⁴, Tengfeng Yan⁵, Chunlei Zhang¹, Ping Hu⁵, Jianqing He¹, Xun Zhu⁶, Xingen Zhu⁵, Yuhai Wang¹

Affiliations

¹ Department of Neurosurgery, 904th Hospital of Joint Logistic Support Force of PLA, Wuxi Clinical College of Anhui Medical University, Wuxi, China.
² Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.
³ Department of Human Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, Hunan Province, China.
⁴ Department of Neurosurgery, Wuxi Huishan Peoples Hospital, Wuxi, Jiangsu, China.
⁵ Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
⁶ Department of Neurosurgery, The Second Hospital of Tianjin Medical University, Tianjin, China.

^# Contributed equally.

Abstract

Introduction: Spontaneous subarachnoid hemorrhage (SAH), is a disorder that may be fatal and is primarily caused by a ruptured brain aneurysm. Despite significant leaps forward in the methods to produce aneurysms, the long-term outcomes did not much improve. Pioglitazone is a medication that has been authorized by the FDA as an agonist for the peroxisome proliferator-activated receptor-gamma (PPARγ). Pioglitazone or PPARγ has neuroprotective benefits in animal experiments both during and after traumatic brain injury (TBI) and SAH. Nevertheless, the treatment impact of Pioglitazone on humans is still unknown at this time. As a result, we will conduct a randomized, double-blind, placebo-controlled trial to explore the impact of pioglitazone on SAH. Methods/Design: This trial will recruit 400 patients with SAH from four Chinese hospitals. These patients will be equally and randomly assigned to Pioglitazone and placebo control groups for up to 30 days. Scores on the modified Rankin scale (mRS) are the primary outcomes. The secondary outcomes are a 30-day all-cause mortality rate, 6 months of Montreal cognitive assessment (Mo-CA), delayed cerebral ischemia, the requirement for intensive care, the incidence of sepsis, etc. All serious adverse events (SAEs) were recorded during the hospital. Every primary and safety analysis was conducted based on the intention-to-treat technique. The participants were given either a matching placebo or 15 mg of pioglitazone, with dose titrated to a target of 45 mg daily. Data on the therapeutic use of pioglitazone after SAH will be provided as a consequence of the findings of this experiment. In addition, this pilot trial is the first to prospectively investigate the effectiveness and safety of pioglitazone in patients with SAH. Ethics and dissemination: Ethics approval was obtained from the Medical Ethics Committee of 904th Hospital of Joint Logistic Support Force of PLA (Wuxi Taihu Hospital, approval No. 20220701). The findings of the trial will be presented at conferences, discussed in relevant patient groups, and published in peer-reviewed journals. Clinical Trial Registration: clinicaltrials.gov, identifier ChiCTR2200062954.

Keywords: PPARγ; SAH; clinical trial; neuroprotection; pioglitazone.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Jiangsu Provincial Natural Science Foundation (Grant No: BK20201140), Hunan Provincial Natural Science Foundation (Grant No: 2023JJ40790), Jiangsu Provincial Natural Science Foundation (Grant No: BK20201140), Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (HB2023130), Wuxi Science and Technology Development Foundation, “Taihu Light” Science and technology Research (Basic research) (Grant No: K20231050).