Safety and Efficacy of Reteplase Versus Alteplase for Acute Ischemic Stroke : A Phase 2 Randomized Controlled Trial
BACKGROUND: Reteplase is a more affordable new-generation thrombolytic with a prolonged half-life. We aimed to determine the safety dose range of reteplase for patients with acute ischemic stroke within 4.5 hours of onset.
METHODS: This is a multicenter, prospective, randomized controlled, open-label, blinded-end point phase 2 clinical trial. Patients with acute ischemic stroke aged between 18 and 80 years who were eligible for standard intravenous thrombolysis were enrolled from 17 centers in China and randomly assigned (1:1:1) to receive intravenous reteplase 12+12 mg, intravenous reteplase 18+18 mg, or intravenous alteplase 0.9 mg/kg. The primary safety outcome was symptomatic intracranial hemorrhage (SITS definition) within 36 hours. The primary efficacy outcome was the proportion of patients with the National Institutes of Health Stroke Scale score of no more than 1 or a decrease of at least 4 points from the baseline at 14 days after thrombolysis.
RESULTS: Between August 2019 and May 2021, 180 patients were randomly assigned to reteplase 12+12 mg (n=61), reteplase 18+18 mg (n=67), or alteplase (n=52). Four patients did not receive the study agent. Symptomatic intracranial hemorrhage occurred in 3 of 60 (5.0%) in the reteplase 12+12 mg group, 1 of 66 (1.5%) in the reteplase 18+18 mg group, and 1 of 50 (2.0%) in the alteplase group (P=0.53). The primary efficacy outcome in the modified intention-to-treat population occurred in 45 of 60 (75.0%) in the reteplase 12+12 mg group (odds ratio, 0.85 [95% CI, 0.35-2.06]), 48 of 66 (72.7%) in the reteplase 18+18 mg group (odds ratio, 0.75 [95% CI, 0.32-1.78]), and 39 of 50 (78.0%) in alteplase group.
CONCLUSIONS: Reteplase was well tolerated in patients with acute ischemic stroke within 4.5 hours of onset in China with a similar efficacy profile to alteplase. The efficacy and appropriate dosage of reteplase for patients with acute ischemic stroke need prospective validation.
REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04028518.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:55 |
|---|---|
| Enthalten in: |
Stroke - 55(2024), 2 vom: 15. Feb., Seite 366-375 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Li, Shuya [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 01.02.2024 Date Revised 01.02.2024 published: Print-Electronic ClinicalTrials.gov: NCT04028518 Citation Status MEDLINE |
|---|
| doi: |
10.1161/STROKEAHA.123.045193 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM366436112 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM366436112 | ||
| 003 | DE-627 | ||
| 005 | 20240202232118.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231229s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1161/STROKEAHA.123.045193 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1278.xml |
| 035 | |a (DE-627)NLM366436112 | ||
| 035 | |a (NLM)38152962 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Li, Shuya |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Safety and Efficacy of Reteplase Versus Alteplase for Acute Ischemic Stroke |b A Phase 2 Randomized Controlled Trial |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.02.2024 | ||
| 500 | |a Date Revised 01.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04028518 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Reteplase is a more affordable new-generation thrombolytic with a prolonged half-life. We aimed to determine the safety dose range of reteplase for patients with acute ischemic stroke within 4.5 hours of onset | ||
| 520 | |a METHODS: This is a multicenter, prospective, randomized controlled, open-label, blinded-end point phase 2 clinical trial. Patients with acute ischemic stroke aged between 18 and 80 years who were eligible for standard intravenous thrombolysis were enrolled from 17 centers in China and randomly assigned (1:1:1) to receive intravenous reteplase 12+12 mg, intravenous reteplase 18+18 mg, or intravenous alteplase 0.9 mg/kg. The primary safety outcome was symptomatic intracranial hemorrhage (SITS definition) within 36 hours. The primary efficacy outcome was the proportion of patients with the National Institutes of Health Stroke Scale score of no more than 1 or a decrease of at least 4 points from the baseline at 14 days after thrombolysis | ||
| 520 | |a RESULTS: Between August 2019 and May 2021, 180 patients were randomly assigned to reteplase 12+12 mg (n=61), reteplase 18+18 mg (n=67), or alteplase (n=52). Four patients did not receive the study agent. Symptomatic intracranial hemorrhage occurred in 3 of 60 (5.0%) in the reteplase 12+12 mg group, 1 of 66 (1.5%) in the reteplase 18+18 mg group, and 1 of 50 (2.0%) in the alteplase group (P=0.53). The primary efficacy outcome in the modified intention-to-treat population occurred in 45 of 60 (75.0%) in the reteplase 12+12 mg group (odds ratio, 0.85 [95% CI, 0.35-2.06]), 48 of 66 (72.7%) in the reteplase 18+18 mg group (odds ratio, 0.75 [95% CI, 0.32-1.78]), and 39 of 50 (78.0%) in alteplase group | ||
| 520 | |a CONCLUSIONS: Reteplase was well tolerated in patients with acute ischemic stroke within 4.5 hours of onset in China with a similar efficacy profile to alteplase. The efficacy and appropriate dosage of reteplase for patients with acute ischemic stroke need prospective validation | ||
| 520 | |a REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04028518 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a humans | |
| 650 | 4 | |a ischemic stroke | |
| 650 | 4 | |a stroke | |
| 650 | 4 | |a thrombolytic therapy | |
| 650 | 4 | |a tissue-type plasminogen activator | |
| 650 | 7 | |a Fibrinolytic Agents |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 650 | 7 | |a reteplase |2 NLM | |
| 650 | 7 | |a DQA630RIE9 |2 NLM | |
| 650 | 7 | |a Tissue Plasminogen Activator |2 NLM | |
| 650 | 7 | |a EC 3.4.21.68 |2 NLM | |
| 700 | 1 | |a Wang, Xuechun |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Aoming |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Gaifen |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Hongqiu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Campbell, Bruce C V |e verfasserin |4 aut | |
| 700 | 1 | |a Fisher, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Junhai |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yilong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xingquan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Liping |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zixiao |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yongjun |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Stroke |d 1970 |g 55(2024), 2 vom: 15. Feb., Seite 366-375 |w (DE-627)NLM000010995 |x 1524-4628 |7 nnns |
| 773 | 1 | 8 | |g volume:55 |g year:2024 |g number:2 |g day:15 |g month:02 |g pages:366-375 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1161/STROKEAHA.123.045193 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 55 |j 2024 |e 2 |b 15 |c 02 |h 366-375 | ||