Stroke, Acute IschemicPhase 2/3ADJUVANT-2NCT06373042
Tirofiban for Successful Endovascular Stroke Thrombectomy
A Phase 2/3 study testing Intraarterial and intravenous tirofiban in people with Stroke, Acute Ischemic, run by Zhongming Qiu.
Trial summary
Up to 50% of acute ischemic stroke patients with large vessel occlusion failed to achieve functional independence even after successful reperfusion therapy, a phenomenon that is referred to as "futile recanalization". Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke, Acute Ischemic
- What is being tested?
- Intraarterial and intravenous tirofiban
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 712 participants
- Where
- No sites listed yet
- Study dates
- 31 Jul 2024to 31 Oct 2026
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical inclusion criteria
- Aged 18 years or older;
- Acute ischemic stroke within 24 hours from last known well to randomization;
- NIHSS score ≥6 and <30 points at baseline;
- Written informed consent is obtained from patients and/or their legal representatives.
- Imaging inclusion criteria
Show all 9Show fewer
- CTA/MRA/DSA showed occlusion of the internal carotid artery, middle cerebral artery M1 or M2 segment;
- For patients within 6 hours from last known well to randomization, ASPECTS 3-10 or infarct volume ≤100ml; 6-24 hours, ASPECTS 6-10 or infarct volume ≤70ml or DWI-FLAIR mismatch;
- Treated with endovascular thrombectomy and achieved successful reperfusion (defined as eTICI grade 2b50 or higher).
Who cannot join
- Cardiogenic embolism;
- Patient receive tirofiban for angioplasty/stenting prior to randomization;
- Intracranial hemorrhage confirmed by flat panel CT on angiography machine prior to randomization;
- Patients who are on prior anticoagulant therapy, e.g. for deep venous thrombosis or pulmonary embolism or mechanical heart valve;
- Routine blood test platelet count less than 100×10⁹/L;
- Renal insufficiency, glomerular filtration rate < 60 mL/min;
Show all 12Show fewer
- Pregnant or lactating women;
- Allergy to tirofiban, contrast agent, nickel, titanium or its alloys;
- History of neurological or psychiatric illness that precludes the assessment of neurological function;
- History of bleeding disorder, severe heart, liver or kidney disease, or sepsis;
- Any terminal illness with life expectancy less than 6 months;
- Participating in other treatment clinical trials.
Trial locations and contacts
No sites are listed yet.
Thanh N. Nguyen, MD contact
About this study
Official title: Efficacy and Safety of Tirofiban Versus Placebo After Successful Reperfusion With Endovascular Thrombectomy in Acute Ischemic Stroke Patients With Anterior Circulation Large Vessel Occlusion: a Multicenter, Double-Blind, Randomized Clinical Trial
Up to 50% of acute ischemic stroke patients with large vessel occlusion failed to achieve functional independence even after successful reperfusion therapy, a phenomenon that is referred to as "futile recanalization". The mechanism of futile recanalization is complex, and some studies have shown that it may be related to factors such as tissue no reflow, reocclusion, poor status of collateral circulation, hemorrhagic transformation, impaired cerebrovascular autonomic regulation, and low perfusion volume. Several studies suggested that maximizing the improvement of cerebral reperfusion is still the primary goal of acute large vessel occlusive stroke. Structural and functional alterations in the microvascular system may be a major obstacle to reperfusion. In animal models of cerebral ischemia, downstream microvascular thrombosis may occur in the early stage of cerebral ischemia and before vascular recanalization, which is the main factor leading to incomplete reperfusion and affecting the efficacy of endovascular thrombectomy.
Mechanical thrombectomy mainly addressed the occluded large arteries, and does not consider the distal arteries. However, the recanalization of occluded large arteries does not necessarily translate into successful reperfusion of the ischemic tissue supplied by the distal capillaries. Even with complete recanalization, impaired microcirculatory reperfusion may lead to poor clinical outcomes. Therefore, we speculate that at the end of endovascular thrombectomy, microthrombi remain present in the microcirculation of brain tissue in patients with complete or near-complete cerebral angiography, and that microthrombi is more likely to be dissolved than thrombus more proximal to the heart. Therefore, intra-arterial administration of pharmaceutical, such as tirofiban, may be the only possible option to ensure complete reperfusion of ischemic tissue. Tirofiban is a platelet glycoprotein IIb/IIIa receptor antagonist, which has been widely used in acute coronary syndrome, and its role in acute ischemic stroke has attracted more and more attention from stroke experts. Previous studies have suggested that tirofiban can further increase the incidence of successful recanalization, while reducing the reocclusion rate.
Whether early administration of intraarterial and intravenous tirofiban can further improve the clinical outcomes of patients with large vessel occlusive stroke after successful mechanical thrombectomy remains unclear.
- Conditions
- Stroke, Acute Ischemic
- Being tested
- Intraarterial and intravenous tirofiban, Intraarterial and intravenous placebo
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intraarterial and intravenous tirofibanDrug
Also called Tirofiban
Intraarterial and intravenous tirofiban after endovascular thrombectomy
Intraarterial and intravenous placeboDrug
Also called Placebo
Intraarterial and intravenous placebo after endovascular thrombectomy
| Study group | Role | What they receive |
|---|---|---|
| Tirofiban | Experimental | Intraarterial and intravenous tirofiban Receives: Drug: Intraarterial and intravenous tirofiban |
| Placebo | Placebo comparator | Intraarterial and intravenous placebo Receives: Drug: Intraarterial and intravenous placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional independence
modified Rankin scale score of 0 to 2. (The modified Rankin scale scores range from 0 to 6, with 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Measured: 90 days post-randomization
Secondary outcomes (12)
Recanalization on follow-up CTA or MRA
Measured with the arterial occlusive lesion (AOL) scale
Measured: within 48 hours post-randomization
Early neurologic improvement
defined as NIHSS score at 48 hours after randomization is reduced by 8 or more compared to NIHSS score at randomization; or the NIHSS at 48 hours after randomization is 0 to 1
Measured: within 48 hours post-randomization
Level of disability
Measured with the mRS
Measured: 90 days post-randomization
Excellent outcome
defined as mRS score of 0-1
Measured: 90 days post-randomization
Independent ambulation
defined as mRS score of 0-3
Measured: 90 days post-randomization
Health-related quality of life
European Quality Five-Dimension Five-Level (EQ-5D-5L) scale score
Measured: 90 days post-randomization
Long-term of disability level
Measured with the mRS
Measured: 1 year post-randomization
Health-related quality of life (long-term)
European Quality Five-Dimension Five-Level (EQ-5D-5L) scale score
Measured: 1 year post-randomization
Incidence of symptomatic intracranial hemorrhage (SICH)
using Heidelberg criteria to assess SICH
Measured: within 48 hours post-randomization
Radiologic intracranial hemorrhage rate
using Heidelberg criteria to assess SICH
Measured: within 48 hours post-randomization
Mortality
Death from any cause
Measured: 90 days post-randomization
Incidence of non-hemorrhagic serious adverse events
such as pneumonia, respiratory failure, circulatory failure, cerebral herniation, secondary epilepsy, sepsis, renal failure, acute coronary syndrome, venous thrombosis, etc
Measured: 90 days post-randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2024
- Study start31 Jul 2024 (estimated)
- Primary completion31 Jul 2026 (estimated)
- Study completion31 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stroke, Acute IschemicStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 712 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhongming Qiu
- Sponsor type
- University, hospital or other
- Collaborators
- Mianyang Central Hospital, The Second Affiliated Hospital of Chongqing Medical University, The Second Hospital of Jiaozuo, Chongzhou People's Hospital, Xihua First Hospital, Xingguo People's Hospital
- Responsible party
- Sponsor-investigator, Zhongming Qiu, Xinqiao Hospital of Chongqing
- Investigators
- Zhongming Qiu, MD, Principal investigator, The 903rd Hospital of PLA, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06373042
- Sponsor's protocol ID
- ADJUVANT-2
- Acronym
- ADJUVANT-2
- Status last verified
- May 2024
- First submitted
- 15 Apr 2024
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: study data without patient information
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Tirofiban Versus Placebo After Successful Reperfusion With Endovascular Thrombectomy in Acute Ischemic Stroke Patients With Anterior Circulation Large Vessel Occlusion: a Multicenter, Double-Blind, Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT06373042
- Acronym / sponsor ID
- ADJUVANT-2 / ADJUVANT-2
- Conditions
- Stroke, Acute Ischemic
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 712 participants (estimated)
- Lead sponsor
- Zhongming QiuUniversity, hospital or other
- Collaborators
- Mianyang Central Hospital, The Second Affiliated Hospital of Chongqing Medical University, The Second Hospital of Jiaozuo, Chongzhou People's Hospital, Xihua First Hospital, Xingguo People's Hospital
- Study start
- 31 Jul 2024 (estimated)
- Primary completion
- 31 Jul 2026 (estimated)
- Study completion
- 31 Oct 2026 (estimated)
- First posted
- 18 Apr 2024 (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.
Up to 50% of acute ischemic stroke patients with large vessel occlusion failed to achieve functional independence even after successful reperfusion therapy, a phenomenon that is referred to as "futile recanalization". The mechanism of futile recanalization is complex, and some studies have shown that it may be related to factors such as tissue no reflow, reocclusion, poor status of collateral circulation, hemorrhagic transformation, impaired cerebrovascular autonomic regulation, and low perfusion volume. Several studies suggested that maximizing the improvement of cerebral reperfusion is still the primary goal of acute large vessel occlusive stroke. Structural and functional alterations in the microvascular system may be a major obstacle to reperfusion. In animal models of cerebral ischemia, downstream microvascular thrombosis may occur in the early stage of cerebral ischemia and before vascular recanalization, which is the main factor leading to incomplete reperfusion and affecting the efficacy of endovascular thrombectomy.
Mechanical thrombectomy mainly addressed the occluded large arteries, and does not consider the distal arteries. However, the recanalization of occluded large arteries does not necessarily translate into successful reperfusion of the ischemic tissue supplied by the distal capillaries. Even with complete recanalization, impaired microcirculatory reperfusion may lead to poor clinical outcomes. Therefore, we speculate that at the end of endovascular thrombectomy, microthrombi remain present in the microcirculation of brain tissue in patients with complete or near-complete cerebral angiography, and that microthrombi is more likely to be dissolved than thrombus more proximal to the heart. Therefore, intra-arterial administration of pharmaceutical, such as tirofiban, may be the only possible option to ensure complete reperfusion of ischemic tissue. Tirofiban is a platelet glycoprotein IIb/IIIa receptor antagonist, which has been widely used in acute coronary syndrome, and its role in acute ischemic stroke has attracted more and more attention from stroke experts. Previous studies have suggested that tirofiban can further increase the incidence of successful recanalization, while reducing the reocclusion rate.
Whether early administration of intraarterial and intravenous tirofiban can further improve the clinical outcomes of patients with large vessel occlusive stroke after successful mechanical thrombectomy remains unclear.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tirofiban | Experimental | Drug: Intraarterial and intravenous tirofibanIntraarterial and intravenous tirofiban |
| Placebo | Placebo comparator | Drug: Intraarterial and intravenous placeboIntraarterial and intravenous placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Clinical inclusion criteria
- Imaging inclusion criteria
Key exclusion criteria (12 listed)
- Cardiogenic embolism;
- Patient receive tirofiban for angioplasty/stenting prior to randomization;
- Intracranial hemorrhage confirmed by flat panel CT on angiography machine prior to randomization;
- Patients who are on prior anticoagulant therapy, e.g. for deep venous thrombosis or pulmonary embolism or mechanical heart valve;
- Routine blood test platelet count less than 100×10⁹/L;
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 |
|---|---|---|
| Intraarterial and intravenous tirofibanAlso: TirofibanIntraarterial and intravenous tirofiban after endovascular thrombectomy | Drug | Tirofiban |
| Intraarterial and intravenous placeboAlso: PlaceboIntraarterial and intravenous placebo after endovascular thrombectomy | Drug | Placebo |
Primary outcome
Functional independence
Time frame: 90 days post-randomization
modified Rankin scale score of 0 to 2. (The modified Rankin scale scores range from 0 to 6, with 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
12 secondary outcomes
Recanalization on follow-up CTA or MRA
Time frame: within 48 hours post-randomization
Early neurologic improvement
Time frame: within 48 hours post-randomization
Level of disability
Time frame: 90 days post-randomization
Excellent outcome
Time frame: 90 days post-randomization
Independent ambulation
Time frame: 90 days post-randomization
Health-related quality of life
Time frame: 90 days post-randomization
Long-term of disability level
Time frame: 1 year post-randomization
Health-related quality of life (long-term)
Time frame: 1 year post-randomization
Incidence of symptomatic intracranial hemorrhage (SICH)
Time frame: within 48 hours post-randomization
Radiologic intracranial hemorrhage rate
Time frame: within 48 hours post-randomization
Mortality
Time frame: 90 days post-randomization
Incidence of non-hemorrhagic serious adverse events
Time frame: 90 days post-randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Individual participant dataSharing planned: Yes. study data without patient information
Related trials for Stroke, Acute Ischemic
Not yet recruiting
Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke
Acute Ischemic Stroke
RecruitingObservational study
ELATE Study: Evaluating Large-vessel Acute Thrombectomy in Extended Time Window
Acute Ichemic Stroke
Not yet recruiting
Selective Intra-Arterial Hypothermia After Endovascular Treatment for Acute Basilar Artery Occlusion
Acute Ischemic Stroke, Basilar Artery Occlusion
RecruitingObservational study
Continuous Dual Aspiration Technique With Zoom System for Stroke
Ischemic Stroke, Acute Stroke
Not yet recruitingPhase 2/3
A Multicenter, Open-label, Randomized, Non-inferiority Clinical Trial With Blinded Endpoint Assessment of Early Tirofiban After Intravenous Thrombolysis in Acute Ischemic Stroke
Acute Ischemic Stroke
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. This study is not recruiting at the moment.
Thanh N. Nguyen, MD contact
Zhongming Qiu, MD principal investigator
The 903rd Hospital of PLA, China
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Intraarterial and intravenous tirofiban in people with Stroke, Acute Ischemic, run by Zhongming Qiu.
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 9 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zhongming Qiu, MD (+8613236599269, qiuzhongmingdoctor@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional independence (time frame: 90 days post-randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 May 2024.