Mild Disabling Acute Ischemic StrokePhase 3BENEFIT-2NCT07369999

Effects of Butylphthalide Enhanced With Tenecteplase on Neurological Function in Mild Disabling Acute Ischemic Stroke

A Phase 3 study testing Combination Group in people with Mild Disabling Acute Ischemic Stroke, run by Xiangya Hospital of Central South University at 15 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Mild Disabling Acute Ischemic Stroke
What is being tested?: Combination Group
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,062 participants
Where: 15 sitesChina
Study dates: 1 Feb 2026to 30 Jun 2029
Phase: Phase 3
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

1. Age 18-80 years, regardless of gender.
2. Clinically diagnosed with acute ischemic stroke and meets the criteria for tenecteplase intravenous thrombolysis.
3. Onset of the current stroke within 4.5 hours.
4. Clinical diagnosis of minor ischemic stroke with a NIHSS score of 2-5, accompanied by persistent unilateral limb weakness or speech symptoms, defined as a score ≥1 on either the language item or any one limb item of the NIHSS
5. Pre-stroke mRS score ≤1.
6. The subject or their legal representative is able and willing to sign the informed consent form.

Who cannot join

1. History of intracranial hemorrhage.
2. Patients who have received or plan to undergo mechanical thrombectomy.
3. History of major head trauma or stroke within the past 3 months.
4. Known severe liver/kidney dysfunction or patients receiving dialysis (severe liver dysfunction: ALT/AST >3 times the upper limit of normal; severe kidney dysfunction: serum creatinine >3.0 mg/dl [265.2 μmol/L] or GFR <30 ml/min/1.73 m²).
5. Systolic blood pressure <90 mmHg or >220 mmHg.
6. Patients with bradycardia (heart rate <60 beats/min) or sick sinus syndrome.

Show all 15Show fewer

7. History of drug/food allergy or known allergy to the components of the study drugs.
8. Patients treated with drugs containing butylphthalide after stroke onset.
9. History of congenital/acquired hemorrhagic diseases, coagulation factor deficiency, or thrombocytopenic diseases.
10. Pregnant or lactating subjects or subjects planning to become pregnant within 90 days.
11. Subjects with severe mental disorders or dementia who cannot cooperate with informed consent and follow-up.
12. Subjects with concurrent malignant tumors or severe systemic diseases, with an expected survival of <90 days.
13. Patients who have participated in other clinical interventional studies within 30 days prior to randomization, or who are currently participating in other clinical interventional studies;
14. Patients who are unable to complete follow-up visits as scheduled;
15. Any other reasons that, in the investigator's opinion, render the patient unsuitable for participation in the study.

Trial locations and contacts

15 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Qiaoling Tang, MD contact

18867408758

228111051@csu.edu.cn

City, postcode or hospital

Sites recruiting now only

15 sites in 1 country

China15 sites, 15 recruiting

Linxiang People's Hospital
Chang’an, Hunan
you Zhan, 13974017299, 13974017299@163.com
Recruiting
Xiangya Hospital, Central South University
Changsha, Hunan, 410600
Le Zhang, +86 139 7318 7150, zlzdzlzd@csu.edu.cn
Zhang, zlzdzlzd@csu.edu.cn
Recruiting
Cili County People's Hospital
Cili, Hunan
qiqiang Peng, 13574433312, 13574433312@163.com
Recruiting
Liuyang Jili Hospital
Guankou, Hunan
玉章贝, 13487494488, 13487494488@163.com
Recruiting
Huayuan County People's Hospital
Huayuan, Hunan
zhiheng Wang, 13739038563, 13739038563@163.com
Recruiting
Lanshan Central Hospital
Lanshan, Hunan
毅黄, 13787614325, 13787614325@163.com
Recruiting
Leiyang People's Hospital
Leiyang, Hunan
少锋雷, 13548521938, 13548521938@163.com
Recruiting
Pingjiang First People's Hospital
Pingjiang, Hunan
Xiang Zeng, 13574008666, 13574008666@163.com
Recruiting
Shaodong People's Hospital
Shaodong, Hunan
Qiong Zhao, 13975970252, 13975970252@163.com
Recruiting
The Central Hospital of Xiangtan, The Affiliated Hospital of Hunan University
Xiangtan, Hunan, 410008
Qun Zeng, Dr., +8613507328587, jiejie61618@163.com
Weimin Jiang, M.Med, +8613789307215, jiangweimin725@163.com
Recruiting
The Third Hospital of Yiyang
Yiyang, Hunan
Zhigao Zhang, 15116302288, 15116302288@163.com
Recruiting
Yizhang County People's Hospital
Yizhang Chengguanzhen, Hunan
勇程, 15873569592, 15873569592@163.com
Recruiting
The Central Hospital of Yongzhou
Yongzhou, Hunan, 410008
Lijin He, 13874690107, tdk1860@vip.sina.com
Sufang Wu, 13707463578, wsfpyn@163.com
Recruiting
Yuanling County People's Hospital
Yuanling, Hunan
Zhi Xiang, 13707459116, 13707459116@163.com
Recruiting
Ningxiang Hospital of Traditional Chinese Medicine
Yutan, Hunan
胜光廖, 13975875378, 13975875378@163.com
Recruiting

Other trials in China

About this study

Official title: Effects of Butylphthalide Enhanced With Tenecteplase on Neurological Function in Mild Disabling Acute Ischemic Stroke -A Prospective, Multicenter, Randomized, Double-blind, Active-controlled Trial

Abstract Background Intravenous thrombolysis is the cornerstone of early treatment for acute ischemic stroke (AIS), but some still have a poor prognosis, especially in patients with mild disabling stroke. Tenecteplase (TNK), a novel thrombolytic agent with favorable pharmacokinetic profiles, and butylphthalide (NBP), a multi-targeted neuroprotective drug, have shown promising efficacy in separate clinical applications. However, evidence for their combined use in mild disabling AIS is lacking.

Aim To determine whether TNK combined with NBP can improve functional outcomes compared with TNK monotherapy in patients with mild disabling AIS who receive thrombolysis within 4.5 hours of onset.

Design BENEFIT-2 is a prospective, multicenter, randomized, double-blind, active-controlled trial. Eligible patients are randomized 1:1 to receive either TNK plus NBP (combination group) or TNK plus placebo (control group) via stratified block randomization. The combination group receives sequential NBP sodium chloride injection (25mg/100ml, twice daily for 7 days) and oral NBP soft capsules (0.2g, three times daily) until day 14; the control group receives matching placebos.

Eligibility criteria include age 18-80 years, onset time ≤4.5 hours, NIHSS score 2-5 with disabling manifestations (hemianopia, aphasia, or limb weakness), and pre-stroke modified Rankin Scale (mRS) score ≤1.

Study outcomes The primary outcome is the proportion of patients with mRS score 0-1 at 90±7 days. Secondary outcomes include changes in NIHSS score, recurrence of ischemic stroke, composite vascular events, quality of life (assessed by EQ-5D scale), and ischemic penumbra salvage rate. Safety outcomes include symptomatic intracranial hemorrhage (sICH), vascular death, all-cause death, and adverse events within 90 days.

Discussion BENEFIT-2 is the first large-scale randomized trial to evaluate the synergistic effect of "vascular recanalization + neuroprotection" in mild disabling AIS. By combining TNK and NBP, this study aims to fill the evidence gap and provide a new therapeutic option to improve functional recovery in this specific population.

Conditions: Mild Disabling Acute Ischemic Stroke
Being tested: Combination Group, Control Group
Keywords: Mild Disabling Acute Ischemic Stroke, Butylphthalide, Tenecteplase

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Combination GroupDrug
Combination Group: TNK 0.25 mg/kg (maximum 25 mg) administered as a single intravenous infusion. Immediately after that, NBP 100 ml (25 mg) is initiated as an intravenous infusion, twice daily (bid), for 7 consecutive days. If the hospitalization duration is less than 7 days, oral NBP soft capsules (0.2 g, three times daily [tid]) will be started on the day of discharge, and continued until Day 14.
Control GroupDrug
Control Group: TNK 0.25 mg/kg (maximum 25 mg) administered as a single intravenous infusion. Immediately after that, a 100 ml intravenous infusion of NBP placebo (visually identical to NBP) is initiated twice daily (bid) for 7 consecutive days. If the hospitalization duration is less than 7 days, oral NBP placebo soft capsules (visually identical, 0.2 g, three times daily [tid]) will be started on the day of discharge and continued until Day 14.

Study groups in NCT07369999
Study group	Role	What they receive
Combination Group	Experimental	Not described Receives: Drug: Combination Group
Control Group	Placebo comparator	Not described Receives: Drug: Control Group

What is being measured

The primary outcome is the main question the study is designed to answer.

Proportion of patients with Modified Rankin Scale score 0-1 (scores 0 = fully asymptomatic to 6 = death)
Measured: From enrollment to the end of treatment at 90 days

Secondary outcomes (9)

proportion of patients with Modified Rankin Scale score 0-2 (scores 0 = fully asymptomatic to 6 = death)
Measured: From enrollment to the end of treatment at 90 days
Proportion of patients with National Institutes of Health Stroke Scale score improvement ≥2 points at 90±7 days compared with baseline. (0-42, higher scores indicate more severe neurological impairment)
Measured: at 90±7 days compared with baseline.
Changes in National Institutes of Health Stroke Scale score from baseline to 6±1 days and 90±7 days. (0-42 points,higher scores indicate more severe neurological impairment)
Measured: From enrollment to 6±1 days and 90±7 days
Incidence of early neurological deterioration (NIHSS score increase ≥4 points) at 24±2 hours and 6±1 days.
Measured: From enrollment to 24±2 hours and 6±1 days.
Recurrence rate of ischemic stroke
Measured: From enrollment to 90±7 days.
Proportion of composite vascular events (stroke recurrence, myocardial infarction, vascular death)
Measured: From enrollment to90±7 days.
Ischemic penumbra salvage rate (change in DWI/PWI mismatch volume from baseline to 6±1 days).
Measured: from baseline to 6±1 days
Quality of life assessed by the EQ-5D scale (utility score and visual analog scale)
Measured: From enrollment to90±7 days.
Stratified composite endpoint: mRS score 0-1 or NIHSS score improvement ≥2 points
Measured: From enrollment to 90±7 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Feb 202630 Jun 2029

First posted27 Jan 2026
Study start1 Feb 2026
Primary completion1 Mar 2029 (estimated)
Study completion30 Jun 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Mild Disabling Acute Ischemic StrokeStudies of the same condition, open and under way.
More trials run by Xiangya Hospital of Central South UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Care provider
Enrolment: 1,062 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07369999
Sponsor's protocol ID: 202512130
Acronym: BENEFIT-2
Status last verified: Jan 2026
First submitted: 8 Jan 2026
Last updated: 3 Aug 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: After publication of the main trial results, de-identified individual participant data and related study documents may be made available on reasonable request to the corresponding author, subject to approval by the Ethics Committee of Xiangya Hospital, Central South University, and in accordance with applicable institutional and ethical requirements.

Publications

Tang Q, Wang L, Tang L, Wang D, Wang D, Li Y, Zhang X, Liu R, Wang S, Zeng Y, Shen M, Zhang L. Butylphthalide combined with tenecteplase in mild disabling acute ischaemic stroke in China (BENEFIT-2): study protocol for a multicentre, randomised, double-blind, active-controlled trial. BMJ Open. 2026 Sep 8;16(9):e119290. doi: 10.1136/bmjopen-2026-119290.
PubMed 42711080

Study at a glance

From the registry record, last updated by the sponsor on 3 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Butylphthalide Enhanced With Tenecteplase on Neurological Function in Mild Disabling Acute Ischemic Stroke -A Prospective, Multicenter, Randomized, Double-blind, Active-controlled Trial
ClinicalTrials.gov ID: NCT07369999
Acronym / sponsor ID: BENEFIT-2 / 202512130
Conditions: Mild Disabling Acute Ischemic Stroke
Keywords: Mild Disabling Acute Ischemic Stroke, Butylphthalide, Tenecteplase
Phase: Phase 3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 1,062 participants (estimated)
Lead sponsor: Xiangya Hospital of Central South UniversityUniversity, hospital or other
Study start: 1 Feb 2026 (actual)
Primary completion: 1 Mar 2029 (estimated)
Study completion: 30 Jun 2029 (estimated)
First posted: 27 Jan 2026 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Aim To determine whether TNK combined with NBP can improve functional outcomes compared with TNK monotherapy in patients with mild disabling AIS who receive thrombolysis within 4.5 hours of onset.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, care provider)
Number of arms: 2

Arm	Type	Receives
Combination Group	Experimental	Drug: Combination Group
Control Group	Placebo comparator	Drug: Control Group

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

1. Age 18-80 years, regardless of gender.
2. Clinically diagnosed with acute ischemic stroke and meets the criteria for tenecteplase intravenous thrombolysis.
3. Onset of the current stroke within 4.5 hours.
4. Clinical diagnosis of minor ischemic stroke with a NIHSS score of 2-5, accompanied by persistent unilateral limb weakness or speech symptoms, defined as a score ≥1 on either the language item or any one limb item of the NIHSS
5. Pre-stroke mRS score ≤1.

Key exclusion criteria (15 listed)

1. History of intracranial hemorrhage.
2. Patients who have received or plan to undergo mechanical thrombectomy.
3. History of major head trauma or stroke within the past 3 months.
4. Known severe liver/kidney dysfunction or patients receiving dialysis (severe liver dysfunction: ALT/AST >3 times the upper limit of normal; severe kidney dysfunction: serum creatinine >3.0 mg/dl [265.2 μmol/L] or GFR <30 ml/min/1.73 m²).
5. Systolic blood pressure <90 mmHg or >220 mmHg.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Combination GroupCombination Group: TNK 0.25 mg/kg (maximum 25 mg) administered as a single intravenous infusion. Immediately after that, NBP 100 ml (25 mg) is initiated as an intravenous infusion, twice daily (bid), for 7 consecutive days. If the hospitalization duration is less than 7 days, oral NBP soft capsules (0.2 g, three times daily [tid]) will be started on the day of discharge, and continued until Day 14.	Drug	Combination Group
Control GroupControl Group: TNK 0.25 mg/kg (maximum 25 mg) administered as a single intravenous infusion. Immediately after that, a 100 ml intravenous infusion of NBP placebo (visually identical to NBP) is initiated twice daily (bid) for 7 consecutive days. If the hospitalization duration is less than 7 days, oral NBP placebo soft capsules (visually identical, 0.2 g, three times daily [tid]) will be started on the day of discharge and continued until Day 14.	Drug	Control Group

Primary outcome

Proportion of patients with Modified Rankin Scale score 0-1 (scores 0 = fully asymptomatic to 6 = death)
Time frame: From enrollment to the end of treatment at 90 days

9 secondary outcomes

proportion of patients with Modified Rankin Scale score 0-2 (scores 0 = fully asymptomatic to 6 = death)
Time frame: From enrollment to the end of treatment at 90 days
Proportion of patients with National Institutes of Health Stroke Scale score improvement ≥2 points at 90±7 days compared with baseline. (0-42, higher scores indicate more severe neurological impairment)
Time frame: at 90±7 days compared with baseline.
Changes in National Institutes of Health Stroke Scale score from baseline to 6±1 days and 90±7 days. (0-42 points,higher scores indicate more severe neurological impairment)
Time frame: From enrollment to 6±1 days and 90±7 days
Incidence of early neurological deterioration (NIHSS score increase ≥4 points) at 24±2 hours and 6±1 days.
Time frame: From enrollment to 24±2 hours and 6±1 days.
Recurrence rate of ischemic stroke
Time frame: From enrollment to 90±7 days.
Proportion of composite vascular events (stroke recurrence, myocardial infarction, vascular death)
Time frame: From enrollment to90±7 days.
Ischemic penumbra salvage rate (change in DWI/PWI mismatch volume from baseline to 6±1 days).
Time frame: from baseline to 6±1 days
Quality of life assessed by the EQ-5D scale (utility score and visual analog scale)
Time frame: From enrollment to90±7 days.
Stratified composite endpoint: mRS score 0-1 or NIHSS score improvement ≥2 points
Time frame: From enrollment to 90±7 days.

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2026.
Derived from this study: PubMed 42711080Tang Q, Wang L, Tang L, Wang D, Wang D, Li Y, Zhang X, Liu R, Wang S, Zeng Y, Shen M, Zhang L. Butylphthalide combined with tenecteplase in mild disabling acute ischaemic stroke in China (BENEFIT-2): study protocol for a multicentre, randomised, double-blind, active-controlled trial. BMJ Open. 2026 Sep 8;16(9):e119290. doi: 10.1136/bmjopen-2026-119290.
Individual participant dataSharing planned: Yes. After publication of the main trial results, de-identified individual participant data and related study documents may be made available on reasonable request to the corresponding author, subject to approval by the Ethics Committee of Xiangya Hospital, Central South University, and in accordance with applicable institutional and ethical requirements.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Qiaoling Tang, MD contact

18867408758

228111051@csu.edu.cn

15 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Combination Group in people with Mild Disabling Acute Ischemic Stroke, run by Xiangya Hospital of Central South University at 15 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 3 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Qiaoling Tang, MD (18867408758, 228111051@csu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients with Modified Rankin Scale score 0-1 (scores 0 = fully asymptomatic to 6 = death) (time frame: From enrollment to the end of treatment at 90 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07369999, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2026.