CHOICE Trial: Adjunct Intra-arterial Alteplase After Successful Thrombectomy
In patients with large vessel occlusion stroke who achieved successful reperfusion (eTICI 2b50 or higher) after thrombectomy, does adjunct intra-arterial alteplase improve excellent functional outcome (mRS 0 to 1) at 90 days compared with placebo?
Renu et al. (JAMA 2022) · 121 patients
Population
Included
- Age 18 years or older
- Acute ischemic stroke from large vessel occlusion treated with thrombectomy within 24 hours of onset
- Successful reperfusion after thrombectomy defined as expanded TICI (eTICI) 2b50 or higher
- Pre-stroke functional independence
- Adjunct intra-arterial alteplase administered immediately after the procedure (0.225 mg/kg, max 22.5 mg, infused over 15 to 30 minutes)
- Symptomatic large vessel occlusion in anterior, middle or posterior cerebral artery treated with mechanical thrombectomy resulting in mTICI score 2b/3, or eligible based on diagnostic angiography before thrombectomy onset
- Estimated delay to onset of rescue intra-arterial rt-PA administration <24 hours from symptom onset
- No significant pre-stroke functional disability (modified Rankin scale 0–1), or mRS >1 unrelated to neurological disease
- Age ≥18 years
- ASPECTS >6 on non-contrast CT (NCCT) or MRI if symptoms lasting <4.5 hours, or ASPECTS >6 on CT-Perfusion (CTP) or DWI-MRI if symptoms >4.5 and <24 hours
- Informed consent from patient or acceptable surrogate
Excluded
- Any contraindication to IV alteplase per local guidelines (other than time to therapy)
- Admission NIHSS greater than 25
- Complete clinical recovery during the angiography procedure
- ASPECTS less than 6 on non-contrast CT if symptom duration was less than 4.5 hours
- Use of oral anticoagulants (a major exclusion in practice)
- NIHSS score on admission >25
- Contraindication to IV t-PA per local national guidelines (except time to therapy)
- Carotid artery stents during procedure requiring dual antiplatelet therapy within first 24 hours
- Pregnant, lactating female, or positive pregnancy test
- Current participation in investigational drug/device studies (except observational studies)
- Hereditary or acquired hemorrhagic diathesis or coagulation factor deficiency
- Known coagulopathy, INR >1.7, or use of novel anticoagulants <48h from symptom onset
- Platelets <50,000
- Renal failure (serum creatinine >3.0 mg/dl or 265.2 μmol/l, or GFR <30)
- Requires hemodialysis/peritoneal dialysis, or contraindication to angiogram
- Any hemorrhage on CT/MRI
- Clinical presentation suggesting subarachnoid hemorrhage
- Suspicion of aortic dissection
- Current or recent history of illicit drug use or alcohol abuse
- Life-threatening allergy to contrast medium (beyond rash)
- SBP >185 mmHg or DBP >110 mmHg refractory to treatment
- Serious, advanced, terminal illness with life expectancy <6 months
- Pre-existing neurological or psychiatric disease confounding evaluation
- Presumed vasculitis or septic embolization
- Unavailable for 90-day follow-up
Source: ClinicalTrials.gov NCT03876119· Retrieved 2026-06-08
Primary Outcome — mRS 0-1 at 90 Days
All randomized patients (LVO, eTICI 2b50+ reperfusion after thrombectomy)
mRS 0-1 at 90 Days
Study Arms
- Agent
- Alteplase (recombinant tissue plasminogen activator), intra-arterial
- Dose
- 0.225 mg/kg (maximum 22.5 mg)
- Route
- Intra-arterial (microcatheter, infused distal to origin of lenticulostriate branches)
- Duration
- Infused over 30 minutes (or over 15 minutes after protocol amendment no. 3, 28 Nov 2019)
- Co-interventions
- Administered immediately after standard mechanical thrombectomy that achieved successful reperfusion (eTICI 2b50–3); given only after the angiographic success criterion was confirmed.
IA alteplase 0.225 mg/kg (max 22.5 mg), distal to lenticulostriate origin, after eTICI 2b50–3 (Renú JAMA 2022 Methods p.828).
- Agent
- Intra-arterial placebo
- Route
- Intra-arterial (microcatheter, injected distally as for active arm)
- Duration
- 15-minute infusion
- Co-interventions
- Administered after the same standard mechanical thrombectomy achieving eTICI 2b50–3; lyophilized placebo (L-arginine phosphate, polysorbate 80) reconstituted in sterile water, injected distal to lenticulostriate origin.
Placebo 15-min IA infusion, identical handling/site, after successful eTICI 2b50–3 (Renú JAMA 2022 Methods p.828).
Trial Design
Type
- Phase 2b randomized double-blind placebo-controlled trial
- Adjunct intra-arterial alteplase after successful thrombectomy
- Large vessel occlusion with eTICI 2b50-3 reperfusion
- Conducted at 7 stroke centers in Catalonia
Timeline
Enrolled 2018-2021; stopped early during the pandemic
N
121
Enrollment
Phase 2b randomized double-blind placebo-controlled trial enrolling 121 patients across 7 stroke centers in Catalonia between 2018 and 2021 (Renu JAMA 2022). Stopped early during the COVID-19 pandemic.
ClinicalTrials.gov
NCT03876119Bedside Pearl
CHOICE is hypothesis-generating, not practice-changing. After successful thrombectomy (eTICI 2b50 or higher), adjunct intra-arterial alteplase improved excellent outcome from 40.4% to 59.0% in 121 patients, but the trial was stopped early during COVID and the lower bound of the 95% CI was 0.3%. Wait for Phase 3 replication before adopting routinely.
See also