---
title: "Bupropion Hydrochloride for Improving Recovery in Acute Ischaemic Stroke: BASE Trial Protocol"
id: "bmj-open-4-protocol-for-base-a-multicentre-double-blind-randomised-controlled-trial-of"
canonical_url: "https://medichelpline.com/clinical-feed/bmj-open-4-protocol-for-base-a-multicentre-double-blind-randomised-controlled-trial-of"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "BMJ Open"
source_url: "http://bmjopen.bmj.com/cgi/content/short/16/7/e116297?rss=1"
published_at: "2026-07-20T14:00:46.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Bupropion Hydrochloride for Improving Recovery in Acute Ischaemic Stroke: BASE Trial Protocol
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/bmj-open-4-protocol-for-base-a-multicentre-double-blind-randomised-controlled-trial-of
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** BMJ Open
- **Source URL:** [Original Journal Publication](http://bmjopen.bmj.com/cgi/content/short/16/7/e116297?rss=1)
- **Published At:** 2026-07-20T14:00:46.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- Stroke poses significant disability and death risks, increasing the need for new recovery treatments. - Bupropion hydrochloride, a norepinephrine–dopamine reuptake inhibitor, is explored for its potential benefits in stroke recovery. - The BASE trial is a multicentre, double-blind, randomized study involving 1054 patients across 40 centers in China. - Participants will be assigned to receive either bupropion (75 mg twice daily) or a placebo for 30 days in addition to standard care. - The primary endpoint evaluates functional recovery, specifically the proportion achieving a modified Rankin Scale (mRS) score of 0–3 at 90 days. - Secondary endpoints include additional scales for neurological progress, quality of life, and safety metrics. - The trial is approved by the Ethics Committee and emphasizes methodological soundness but notes potential limitations in broader applicability due to strict criteria.
## Clinical Analysis & Structured Key Points
Skip to main content Intended for healthcare professionals Log In Basket Search for this keyword Advanced search Latest content Archive For authors About Browse by collection You are here Home Archive Volume 16, Issue 7 Email alerts Article Text Article info Citation Tools Share Rapid Responses Article metrics Alerts PDF Neurology Protocol Protocol for BASE: a multicentre, double-blind, randomised, controlled trial of bupropion hydrochloride in acute ischaemic stroke in China Qisheng Cheng1, Yuxin Ran1, Dongfang Wang1, Wensong Yang2, Yiqing Shen2, Yikun Ren1,3, Huiji Zhang1, Yajie Xiang1, Huan Wang2, Jing Wang4,5, Jing Guo4,5, Chuyue Wu4,5, http://orcid.org/0009-0006-6531-0474Shengli Chen4,5, Hao Li6, Wei Li7, Pu Zhang1, Dan Liu1, Qian Zhou1, http://orcid.org/0000-0002-9144-148XQi Li2, Peng Zheng2, Zicheng Hu2, http://orcid.org/0000-0002-0081-6048Peng Xie1 Correspondence to Professor Peng Xie; xiepeng@cqmu.edu.cn; Professor Zicheng Hu; 39128522@qq.com Abstract Introduction Stroke remains a leading cause of disability and mortality worldwide, with an urgent need for novel therapeutic strategies to improve recovery. Bupropion hydrochloride, a norepinephrine–dopamine reuptake inhibitor, may promote motor and cognitive recovery due to its unique mechanism of action. To evaluate the efficacy and safety of early adjunctive treatment with bupropion hydrochloride versus placebo on functional recovery in patients with acute ischaemic stroke. Methods and analysis BASE is an investigator-initiated, multicentre, randomised, double-blind, placebo-controlled trial. We plan to enrol 1054 eligible patients with acute ischaemic stroke (National Institutes of Health Stroke Scale (NIHSS) score 8–15, within 2–7 days after onset) from approximately 40 stroke centres across China. Participants will be randomly assigned (1:1) to receive either oral bupropion hydrochloride (75 mg two times per day) or matched placebo for 30 days, in addition to standard guideline-based care. The primary efficacy endpoint is the proportion of patients achieving a favourable functional outcome, defined as a modified Rankin Scale (mRS) score of 0–3 at 90 days. Key secondary endpoints include shifts in mRS scores, changes in NIHSS, Hamilton Depression Rating Scale (HAMD-17), Fugl-Meyer Motor Scale scores and quality of life (EQ-5D). Safety endpoints include mortality, vascular events and incidence of adverse events. Analyses will be performed on both the intention-to-treat and per-protocol populations Ethics and dissemination The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (ID ZZ2025-747-01), and all participants will provide written informed consent. Results will be disseminated through peer-reviewed publications and conference presentations. Trial registry number ChiCTR2500105746 (www.chictr.org.cn). https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/. https://doi.org/10.1136/bmjopen-2026-116297 Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. Request permissions STRENGTHS AND LIMITATIONS OF THIS STUDY This study employs a rigorous multicentre, randomised, double-blind, placebo-controlled design. By focusing on patients with moderate stroke severity (National Institutes of Health Stroke Scale (NIHSS) 8–15), the study enhances the ability to detect a treatment signal. The sample size is adequately powered to detect a clinically meaningful difference in the primary functional outcome. A comprehensive set of standardised and clinically relevant outcome measures, including functional, neurological, motor and quality-of-life scales, will provide a multidimensional assessment of recovery. The strict exclusion criteria and protocol-prohibited use of concomitant antidepressants, while methodologically sound for establishing efficacy, may limit the wider application of the research results in routine clinical practice for the stroke patient population. Background Stroke is a leading cause of death and long-term disability worldwide. The therapeutic impact of reperfusion therapies (thrombolysis and thrombectomy) is limited by narrow time windows and eligibility, benefiting only a small fraction of patients.1 Numerous neuroprotective agents have failed to demonstrate efficacy in clinical trials.2 Current secondary prevention rests on the established triad of antiplatelet agents, statins (lipid-lowering) and antihypertensives (the antiplatelet agents, statins and antihypertensives approach),3 highlighting the urgent need for novel strategies to improve poststroke recovery. Growing evidence indicates that depression is not merely a consequence of stroke but also an independent risk factor for its initial occurrence and recurrence, playing a critical role throughout the course of the disease.4 Therefore, interventions targeting modifiable risk factors—such as statins for dyslipidaemia and antihypertensive agents—constitute the foundation of standard preventive care, supported by robust randomised controlled trial (RCT) data. Interestingly, the potential role of antidepressants in poststroke recovery has attracted increasing attention. Several RCTs investigating the early use of antidepressants such as fluoxetine or citalopram have reported enhanced motor cortex excitability along with improvements in motor and neurological function.5–7 However, these findings are not consistent. Dam et al study1 and FLAME study8 have shown that the early use of fluoxetine facilitated the recovery of patients with stroke. Three major recent RCTs (FOCUS, EFFECTS, AFFINITY) showed that fluoxetine did not significantly improve functional outcomes as assessed by the modified Rankin Scale (mRS) at 6 months, although it proved effective in preventing poststroke depression.9–11 Heterogeneity in baseline patient characteristics, particularly stroke severity, may account for the discrepant findings across these trials (mean National Institutes of Health Stroke Scale (NIHSS) 12.8 in the positive FLAME trial vs 3–6 in the other trials). The varying effects of specific antidepressants provide a promising direction for further research. For example, citalopram appears to selectively enhance motor cortex excitability, whereas fluoxetine exerts broader neuromodulatory effects.8 Bupropion, a norepinephrine-dopamine reuptake inhibitor (NDRI), has a distinct mechanism of action that may overcome certain limitations associated with selective serotonin reuptake inhibitors (SSRIs). Its action on the dopaminergic system, critically involved in motor control, motivation and reward, provides a theoretical basis for potentially promoting motor and cognitive recovery more effectively than serotonergic agents. Preliminary evidence in major depression indicates bupropion can rapidly improve energy, interest and anhedonia.12–14 Preclinical studies have shown that bupropion can improve the neurological behaviour scores of rats after ischaemia-reperfusion.15 However, its efficacy and safety in the context of acute stroke recovery have not been established in an RCT. This study aims to investigate whether early adjunctive treatment with bupropion hydrochloride can improve functional outcomes in patients with acute ischaemic stroke. Methods and analysis Trial design The Bupropion Hydrochloride for Acute Ischemic Stroke Recovery Trial is a prospective, multicentre, randomised, double-blind, placebo-controlled, parallel-group study. This trial will be conducted in accordance with the principles of the Declaration of Helsinki and has been registered at www.chictr.org.cn (registration number: ChiCTR2500105746). This clinical trial has not yet begun recruitment and is expected to last from 2026 to 2029. It is expected to be conducted in the following hospitals: The First Affiliated Hospital of Chongqing Medical University, The Affiliated YongChuan Hospital of Chongqing Medical University, Chongqing University Three Gorge Hospital, People’s Hospital of Jianyang City, The First People’s Hospital of Changde City, Chongqing Kaizhou Hospital of Traditional Chinese Medicine, The Ninth People’s Hospital of Chongqing, The Second Hospital of Hebei Medical University, The People’s Hospital of Chongqing Hechuan District, Bazhong Central Hospital, The Third People’s Hospital of Mianyang City, Suining Central Hospital, Guizhou Provincial People’s Hospital, The Affiliated Hospital of Guizhou Medical University, The People’s Hospital of Chongqing Rongchang District, The Fifth Affiliated Hospital of Southern Medical University, The People’s Hospital of Chongqing Dazu District, Chongqing University Fuling Hospital, The People’s Hospital of Chongqing Changshou District, The People’s Hospital of Chongqing Yubei District, The People’s Hospital of Chongqing Tongliang District, The People’s Hospital of Chongqing Liangping District, The People’s Hospital of Chongqing Dianjiang District, The People’s Hospital of Chongqing Xiushan District, The People’s Hospital of Chongqing Banan District. Due to the individualised policies of local hospitals, the number of centres may increase or decrease when the project is officially launched. Written informed consent was obtained from all enrolled patients or their legal representatives prior to randomisation (online supplemental material). The patient flow diagram is shown in figure 1. Supplemental material [bmjopen-2026-116297supp001.pdf] Download figure Open in new tab Download powerpoint Figure 1 Trial design and treatment flow diagram. ASA, antiplatelet agents, statins and antihypertensives; EQ-5D, EuroQol Five Dimensions Questionnaire; FMMS, Fugl-Meyer motor scale; HAMD-17, Hamilton Depression Rating Scale; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale. Patient and public involvement Patients and the public were not directly involved in the design and conception of the study. Patient population Inclusion criteria Patients clinically diagnosed with acute cerebral infarction. Those who have received standard intravenous thrombolysis for the current stroke episode may also be included if their symptoms do not worsen after thrombolysis and before trial medication. Diagnostic criteria are based on the WHO definition of stroke: acute onset of focal or global neurological deficit with clinical signs persisting for more than 24 hours. Age ≥18 years, regardless of gender. NIHSS score between 8 and 15 (inclusive) at enrolment. Limb muscle strength grade ≤3. Hospitalised patients within 2–7 days after the onset of the current stroke. Prestroke functional independence (prestroke mRS score ≤1). Signed informed consent obtained from the participant or their legal guardian. Exclusion criteria Patients who have undergone endovascular mechanical thrombectomy for the current stroke episode. Stroke or cerebral dysfunction due to other non-vascular causes (primary brain tumour, brain metastasis, subdural haematoma, traumatic brain injury). History of dementia or psychiatric disorders other than depression. Severe impairment of consciousness (NIHSS item 1a ‘Level of Consciousness’ score >1) or inability to complete assessments due to visual, hearing, language or comprehension deficits. Stroke attributable to other specific aetiologies (cerebral arteritis, arterial dissection, migraine with aura/vasospasm, drug or alcohol abuse). Transient ischaemic attack, reversible ischaemic neurological deficit or subarachnoid haemorrhage. Coexisting neurological diseases such as Parkinson’s disease, epilepsy, Alzheimer’s disease or central nervous system infections (HIV, syphilis). Patients who have received or are scheduled to receive physical therapies such as electroconvulsive therapy. Severe hepatic or renal dysfunction: ALT or AST>2× upper limit of normal; serum creatinine >2.0 mg/dL or >176.8 µmol/L. Severe pulmonary diseases, including lung cancer, tuberculosis, asthma, chronic obstructive pulmonary disease, pulmonary embolism, acute exacerbation of chronic bronchitis, chronic cor pulmonale, pulmonary encephalopathy, acute bronchitis, emphysema, viral pneumonia, interstitial pneumonia, etc. Uncontrolled hypertension despite active antihypertensive treatment: systolic blood pressure (SBP) ≥180 mm Hg or diastolic blood pressure (DBP) ≥100 mm Hg. Severe dysglycaemia: blood glucose 22.2 mmol/L. Any known coagulation disorder, such as current use of vitamin K antagonists with international normalised ratio (INR) >1.7 or prothrombin time >15 s; use of direct thrombin inhibitors or novel oral anticoagulants within the past 48 hours (unless reversal with idarucizumab is applicable); or laboratory values exceeding the upper limit of normal (activated partial thromboplastin time (aPTT), INR, platelet count, thrombin time (TT) or appropriate factor Xa activity assay); or elevated aPTT above the upper limit of normal within the past 24 hours while on heparin. Known platelet dysfunction or platelet count <100×10⁹/L (patients on antiplatelet therapy may be included). Coexisting conditions affecting limb motor function (claudication, osteoarthritis, rheumatoid arthritis, gouty arthritis) that may interfere with neurological examination. Inability to perform activities of daily living independently prior to the current stroke due to other illnesses or frailty, which could significantly affect efficacy evaluation. Inability to swallow oral medication. History of allergy or contraindication to bupropion. Use of other antidepressant medications within the past 3 months or currently. Use of bupropion or other antidepressants after the current stroke onset. Pregnancy, lactation or plan to become pregnant within 90 days. Concurrent malignant tumour or serious illness with a life expectancy of less than 1 year. Participation in another interventional clinical trial within 3 months before randomisation or current participation in such a trial. Any other condition that, in the investigator’s judgement, would affect patient compliance or completion of follow-up. Randomisation and blinding Eligible participants will be randomly assigned in a 1:1 ratio to the bupropion group or the placebo group. The randomisation sequence will be computer-generated using stratified block randomisation by centre. An independent statistician will prepare the allocation sequence. All study personnel, investigators, outcome assessors, data managers, statisticians and participants will be blinded to treatment assignment throughout the trial. The bupropion and placebo tablets will be identical in appearance, packaging and labelling. Interventions Bupropion group Participants will receive oral bupropion hydrochloride tablets (75 mg, manufactured by Venturepharm (Hainan) Co, brand name: Lefuting) two times per day (morning and evening) for 30 days, in addition to standard guideline-based care. Placebo group Participants will receive identically matched placebo tablets on the same schedule, along with standard care. Standard care All participants will receive guideline-based management for acute ischaemic stroke, including antiplatelet therapy (aspirin, clopidogrel), statins and management of vascular risk factors (hypertension, diabetes, etc), as determined by the treating neurologist. The use of other antidepressant medications during the 30-day treatment period is prohibited unless specifically required for emerging depressive symptoms, in which case open-label bupropion may be provided. Study procedures and follow-up Assessments will be conducted at baseline (including demographics, medical history, NIHSS, Hamilton Depression Rating Scale (HAMD)-17, Fugl-Meyer Motor Scale and prestroke mRS), day 7 (or predischarge), day 30 and day 90. Follow-up visits will include assessments of mRS, NIHSS, adverse event (AEs) monitoring and concomitant medication review. The HAMD-17, Fugl-Meyer and EQ-5D assessments will be repeated at day 90. A schedule of events is provided in the protocol (table 1). VIEW INLINE VIEW POPUP Table 1 Schedule of events Outcomes Primary efficacy endpoint Proportion of participants with a favourable functional outcome (mRS score 0–3) at 90 days. Secondary efficacy endpoints Proportion with functional independence (mRS 0–2) at 30 and 90 days. Proportion with significant neurological improvement (NIHSS reduction ≥4 points or score 0–1) at day 7, 30 and 90. Change from baseline to day 90 in HAMD-17 score. Change from baseline to day 90 in limb muscle strength and Fugl-Meyer Motor Scale score. Quality of life assessed by EQ-5D at day 90. Safety endpoints All-cause mortality at 90 days; incidence of vascular events (recurrent stroke, Myocardial Infarction, vascular death); incidence of all AEs and treatment-related AEs, including falls and fractures. Prespecified management and intervention procedures for specific risks In light of the known potential risks associated with the investigational drug bupropion, this study establishes the following targeted, proactive monitoring and standardised management plans to ensure subject safety. Management of hypertension risk Definitions and classification Clinically significant blood pressure elevation: an increase in blood pressure requiring initiation of new antihypertensive therapy or intensification of the existing regimen. Classification criteria: Grade 1 (alert): systolic blood pressure (SBP)≥160 mm Hg and/or DBP≥100 mm Hg, but <180/110 mm Hg and asymptomatic. Grade 2 (requiring intervention): SBP ≥180 mm Hg and/or DBP≥110 mm Hg; OR any blood pressure level accompanied by new or worsening symptoms suggestive of hypertension (eg, severe headache, blurred vision, chest pain, dyspnoea). Monitoring protocol Frequency: baseline (at least two measurements averaged within 24 hours prerandomisation), during the first 7 days of treatment (at least once daily), at each scheduled visit, and on symptom presentation. Standardisation: measurements shall be taken using calibrated devices after the subject has rested quietly for at least 5 min. The average of two readings should be recorded. Standardised intervention pathway All recorded blood pressure values will be evaluated and managed according to the following pathway. First, each measurement is assessed and classified. For grade 1 elevations without symptoms, monitoring frequency is increased, the current study treatment is continued and optimisation of background antihypertensive therapy may be considered. If grade 2 criteria are met or symptoms occur, immediate clinical evaluation is performed to determine if a hypertensive emergency (with evidence of target organ damage) is present. Confirmation of a hypertensive emergency necessitates immediate suspension of the investigational drug, urgent medical referral and reporting as a serious AE (SAE). For non-emergent grade 2 elevations, a stepwise intervention is initiated. The first step involves intensification of background antihypertensive therapy by the investigator according to clinical guidelines. If blood pressure remains uncontrolled after 1–3 days of optimised therapy, the dose of the investigational drug is reduced (from 75 mg two times per day to 75 mg/day). Should elevated blood pressure persist despite dose reduction, the investig
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