Ginkgolide With Intravenous Alteplase Thrombolysis in Acute Ischemic Stroke Improving Neurological Function: A Multicenter, Cluster-Randomized Trial (GIANT)

Abstract

Background and Purpose: We aimed to investigate the effect of Ginkgolide® treatment on neurological function in patients receiving intravenous (IV) recombinant tissue plasminogen activator (rt-PA).Methods: This cluster randomized controlled trial included acute ischemic stroke patients in 24 centers randomized to intervention of intravenous Ginkgolide® or control group within the first 24 h after IV rt-PA therapy (IVT). Clinical outcome at 90 days was assessed with modified Rankin Scale (mRS) score and dichotomized into good outcome (0–2) and poor outcome (3–6). Hemorrhagic transformation represented the conversion of a bland infarction into an area of hemorrhage by computed tomography. Symptomatic intracerebral hemorrhage (sICH) was defined as cerebral hemorrhagic transformation in combination with clinical deterioration of National Institutes of Health Stroke Scale (NIHSS) score ≥4 points at 7-day or if the hemorrhage was likely to be the cause of the clinical deterioration. We performed logistic regression analysis and propensity score matching analysis to investigate the impact of Ginkgolide® treatment with IV rt-PA on good outcome, hemorrhagic transformation and sICH, respectively.Results: A total of 1113 patients were finally included and 513 (46.1%) were in the intervention group. Patients in the Ginkgolide® group were more likely to have good outcomes (78.6 vs. 66.7%, p < 0.01) and lower rate of sICH (0 vs. 2.72%, p < 0.01), compared with patients in the control group. The intra-cluster correlation coefficient (ICC) for good outcome at 90 days was 0.033. Binary logistic regression analysis revealed that treatment with Ginkgolide® was independently associated with 90-day mRS in patients with IV rt-PA therapy (OR 1.498; 95% CI 1.006–2.029, p = 0.009). After propensity score matching, conditional logistic regression showed intervention with Ginkgolide® was significantly associated with 90-day good outcome (OR 1.513; 95% CI 1.073–2.132, p = 0.018). No significant difference in hemorrhage transformation was seen between the 2 matched cohorts (OR 0.885; 95% CI 0.450–1.741, p = 0.724).Conclusion: Using Ginkgolide® within 24-hour after IV rt-PA is effective and safe and might be recommended in combination with rtPA therapy in acute ischemic stroke.Clinical Trial Registration:http://www.clinicaltrials.gov, identifier NCT03772847.

Efficient Sustained-Release Nanoparticle Delivery System Protects Nigral Neurons in a Toxin Model of Parkinson’s Disease

“…As such, GB treatment can protect against 6-hydroxydopamine-induced neurotoxic cell death among dopaminergic neurons. GB and Ginkgo biloba extract are also used clinically for the treatment of dementia and ischemic stroke [6,7]. However, GB water solubility is very poor and it exhibits very low bioavailability when administered orally, preventing it from accumulating at high levels in the systemic circulation and brain, thereby impeding its clinical anti-Parkinsonian utilization [8][9][10].…”

Anti-atherosclerotic effects and molecular targets of ginkgolide B from Ginkgo biloba

“… Registration No. Recruitment status Study title Target disease Phase Interventions CTR20200390 Completed A phase I clinical trial to evaluate the safety and tolerability of single and multiple intravenous ginkgolide B injections in healthy Chinese subjects Acute ischemic stroke Ⅰ Ginkgolide B injection CTR20200487 Recruiting A phase I clinical study to evaluate the safety, tolerability, and pharmacokinetics of ginkgolide B injection in healthy Chinese volunteers Acute ischemic stroke Ⅰ Ginkgolide B injection ChiCTR-IPR-17012310 Recruiting Ginkgolide in ischemic stroke patients with large artery atherosclerosis (GISAA) 193 Stroke IV Ginkgolide injection + oral aspirin NCT03772847 Completed Ginkgolide with intravenous alteplase thrombolysis in acute ischemic stroke neurological improving trial 200 Intravenous alteplase thrombolysis Neurological improving IV Ginkgolide plus alteplase ChiCTR-ONC–13003247 Completed A multicenter clinical trial assessment of Baiyu Ginkgolide injection, in the treatment of ischemic stroke with blood stasis syndrome Ischemic stroke IV Baiyu Ginkgolide injection NCT01958957 Completed A safety study of ginkgolides meglumine injection in the treatment of ischemic stroke Ischemic stroke IV Ginkgolides Meglumine Injection CTR20160610 Completed Single and multiple administration of dimethylaminoethyl ginkgolide B mesylate tablets in a randomized double-blind placebo-controlled PK/PD study and the effect of eating on PK/PD Acute ischemic cerebrovascular disease Ⅰ Dimethylaminoethyl ginkgolide B mesylate tablets CTR20140805 Completed Research protocol of multiple administration, dose-escalation, randomized, double-blind, placebo-controlled phase I clinical trial of dimethylaminoethyl ginkgolide B mesylate injection Acute ischemic stroke Ⅰ Dimethylaminoethyl ginkgolide B mesylate injection CTR20210113 Recruiting A phase I clinical study on the safety, tolera...…”