ArticleClinical trials (London, England)2022
An adaptive clinical trial design to identify the target dose of tenecteplase for treatment of acute pulmonary embolism.
Article in Clinical trials (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed, 4 citations in OpenAlex.
- The effect of rivaroxaban as an anticoagulant therapy for acute pulmonary embolism and the predictive role of vascular endothelial markers in assessing anticoagulant efficacy before treatment.American journal of translational research · 2025Article
- Comparison of Treatment Approaches and Subsequent Outcomes within a Pulmonary Embolism Response Team Registry.Critical care research and practice · 2024Article
Corrections and comments
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Authors and funding
9 authors at 7 institutions in 1 country.
Funding
Abstract
BACKGROUND/
aimsFibrinolytic therapy with tenecteplase has been proposed for patients with pulmonary embolism but the optimal dose is unknown. Higher-than-necessary dosing is likely to cause excess bleeding. We designed an adaptive clinical trial to identify the minimum and assumed safest dose of tenecteplase that maintains efficacy.
methodsWe propose a Bayesian adaptive, placebo-controlled, group-sequential dose-finding trial using response-adaptive randomization to preferentially allocate subjects to the most promising doses, dual analyses strategies (continuous and dichotomized) using a gatekeeping approach to maximize clinical impact, and interim stopping rules to efficiently address competing trial objectives. The operating characteristics of the proposed design were evaluated using Monte Carlo simulation across multiple hypothetical efficacy scenarios.
resultsSimulation demonstrated response-adaptive randomization can preferentially allocate subjects to doses which appear to be performing well based on interim data. Interim decision-making, including the interim evaluation of both analysis strategies with gatekeeping, allows the trial to continue enrollment when success with the dichotomized analysis strategy appears sufficiently likely and to stop enrollment and declare superiority based on the continuous analysis strategy when there is little chance of ultimately declaring superiority with the dichotomized analysis.
conclusionThe proposed design allows evaluation of a greater number of dose levels than would be possible with a non-adaptive design and avoids the need to choose either the continuous or the dichotomized analysis strategy for the primary endpoint.
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