Tenecteplase versus alteplase for large vessel occlusion recanalization (T-FLAVOR): Trial protocol

Hiroyuki Kawano; Teruyuki Hirano; Manabu Inoue; Mayumi Fukuda-Doi; Koji Iwasaki; Katsuhiro Omae; Kanta Tanaka; Haruko Yamamoto; Masatoshi Koga; Nobuyuki Sakai; Takehiko Nagao; Makoto Sasaki; Naoki Hayakawa; Kazunori Toyoda

doi:10.1177/23969873211070455

Tenecteplase versus alteplase for large vessel occlusion recanalization (T-FLAVOR): Trial protocol

Eur Stroke J. 2022 Mar;7(1):71-75. doi: 10.1177/23969873211070455. Epub 2022 Jan 7.

Authors

Affiliations

¹ Department of Stroke and Cerebrovascular Medicine, Kyorin University, Tokyo, Japan.
² Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
³ Department of Data Science, National Cerebral and Cardiovascular Center, Suita, Japan.
⁴ Academic Clinical Research Center, Department of Medical Innovation, Osaka University Hospital, Suita, Japan.
⁵ Department of Neurosurgery, Kobe City Medical Center General Hospital, Kobe, Japan.
⁶ Department of Neurology, Nippon Medical School Tamanagayama Hospital, Tama, Japan.
⁷ Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Morioka, Japan.
⁸ Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Japan.

Abstract

Background: Tenecteplase has higher fibrin specificity with a longer half-life and the potential to achieve higher rates of recanalization than alteplase. A critical limitation of tenecteplase is no commercial use in Japan and no experience with its administration to Japanese patients.

Hypothesis: Tenecteplase is superior to alteplase in achieving recanalization on the initial angiogram when administered ≤4.5-hour of stroke onset in patients planned for mechanical thrombectomy (MT) in Japan where alteplase at the unique dose of 0.6mg/kg is officially used.

Methods: The Tenecteplase versus alteplase For LArge Vessel Occlusion Recanalization (T-FLAVOR) trial is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, masked-endpoint, superiority study. Eligibility criteria include acute ischemic stroke with pre-stroke modified Rankin Scale score ≤3 and large vessel occlusion (internal carotid artery, middle cerebral artery, or basilar artery) eligible for intravenous thrombolysis ≤4.5-hour and MT ≤6-hour of stroke onset. After completing the safety confirmation phase involving three patients who received non-masked tenecteplase (0.25 mg/kg), 220 patients will be randomized to two groups (1:1), intravenous alteplase (0.6mg/kg, n = 110) or tenecteplase (0.25mg/kg, n = 110), prior to MT.

Outcomes: In the safety confirmation phase, the primary outcome is symptomatic intracranial hemorrhage (sICH) ≤24-36-hour. In the randomized, comparative phase, the primary efficacy outcome is substantial angiographic reperfusion (mTICI grade 2b/2c/3) or absence of retrievable thrombus on the initial angiogram. The primary safety outcome is sICH ≤24-36-hour and 90-day mortality.

Discussion: T-FLAVOR may help determine if tenecteplase should be recommended as a routine clinical strategy before MT for Japanese stroke patients.

Trial registration: jRCTs051210055.

Keywords: Ischemic stroke; alteplase; mechanical thrombectomy; randomized trial; tenecteplase; thrombolysis; tissue plasminogen activator.