Microbubbles and UltraSound-accelerated Thrombolysis (MUST) for peripheral arterial occlusions: Protocol for a phase II single-arm trial

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Introduction Acute peripheral arterial occlusions can be treated with intra-arterial catheter-directed thrombolysis as an alternative to surgical thromboembolectomy. Although less invasive, this treatment is time-consuming and carries a significant risk of haemorrhagic complications. Contrast-enhanced ultrasound using microbubbles could accelerate dissolution of thrombi by thrombolytic medications due to mechanical effects caused by oscillation; this could allow for lower dosages of thrombolytics and faster thrombolysis, thereby reducing the risk of haemorrhagic complications. In this study, the safety and practical applicability of this treatment will be investigated. Methods and analysis A single-arm phase II trial will be performed in 20 patients with acute peripheral arterial occlusions eligible for thrombolytic treatment. Low-dose catheter-directed thrombolysis with urokinase will be used. The investigated treatment will be performed during the first hour of thrombolysis, consisting of intravenous infusion of 4 Luminity phials (6 mL in total, diluted with saline 0.9% to 40 mL total) of microbubbles with the use of local ultrasound at the site of occlusion. Primary end points are the incidence of complications and technical feasibility. Secondary end points are angiographic and clinical success, duration of thrombolytic infusion, treatment-related mortality, amputations, additional interventions and quality of life. Ethics and dissemination Ethical approval for this study was obtained in 2015 from the Medical Ethics Committee of the VU University Medical Center, Amsterdam, the Netherlands. A statement of consent for this study was given by the Dutch national competent authority. Data will be presented at national and international conferences and published in a peer-reviewed journal. Trial registration numbers Dutch National Trial Registry: NTR4731; European Clinical Trials Database of the European Medicines Agency: 2014-003469-10; Pre-results.

Original languageEnglish
Article numbere014365
JournalBMJ Open
Volume7
Issue number8
DOIs
Publication statusPublished - 1 Aug 2017

Cite this

@article{465461780abf40a3913d93098c9daa57,
title = "Microbubbles and UltraSound-accelerated Thrombolysis (MUST) for peripheral arterial occlusions: Protocol for a phase II single-arm trial",
abstract = "Introduction Acute peripheral arterial occlusions can be treated with intra-arterial catheter-directed thrombolysis as an alternative to surgical thromboembolectomy. Although less invasive, this treatment is time-consuming and carries a significant risk of haemorrhagic complications. Contrast-enhanced ultrasound using microbubbles could accelerate dissolution of thrombi by thrombolytic medications due to mechanical effects caused by oscillation; this could allow for lower dosages of thrombolytics and faster thrombolysis, thereby reducing the risk of haemorrhagic complications. In this study, the safety and practical applicability of this treatment will be investigated. Methods and analysis A single-arm phase II trial will be performed in 20 patients with acute peripheral arterial occlusions eligible for thrombolytic treatment. Low-dose catheter-directed thrombolysis with urokinase will be used. The investigated treatment will be performed during the first hour of thrombolysis, consisting of intravenous infusion of 4 Luminity phials (6 mL in total, diluted with saline 0.9{\%} to 40 mL total) of microbubbles with the use of local ultrasound at the site of occlusion. Primary end points are the incidence of complications and technical feasibility. Secondary end points are angiographic and clinical success, duration of thrombolytic infusion, treatment-related mortality, amputations, additional interventions and quality of life. Ethics and dissemination Ethical approval for this study was obtained in 2015 from the Medical Ethics Committee of the VU University Medical Center, Amsterdam, the Netherlands. A statement of consent for this study was given by the Dutch national competent authority. Data will be presented at national and international conferences and published in a peer-reviewed journal. Trial registration numbers Dutch National Trial Registry: NTR4731; European Clinical Trials Database of the European Medicines Agency: 2014-003469-10; Pre-results.",
keywords = "microbubbles, peripheral arterial occlusion, sonothrombolysis, thrombolysis, ultrasound",
author = "Ebben, {Harm P.} and Nederhoed, {Johanna H.} and Lely, {Rutger J.} and Willem Wisselink and Kakkhee Yeung and {on behalf of the MUST collaborators}",
year = "2017",
month = "8",
day = "1",
doi = "10.1136/bmjopen-2016-014365",
language = "English",
volume = "7",
journal = "BMJ Open",
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Microbubbles and UltraSound-accelerated Thrombolysis (MUST) for peripheral arterial occlusions : Protocol for a phase II single-arm trial. / Ebben, Harm P.; Nederhoed, Johanna H.; Lely, Rutger J.; Wisselink, Willem; Yeung, Kakkhee; on behalf of the MUST collaborators.

In: BMJ Open, Vol. 7, No. 8, e014365, 01.08.2017.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Microbubbles and UltraSound-accelerated Thrombolysis (MUST) for peripheral arterial occlusions

T2 - Protocol for a phase II single-arm trial

AU - Ebben, Harm P.

AU - Nederhoed, Johanna H.

AU - Lely, Rutger J.

AU - Wisselink, Willem

AU - Yeung, Kakkhee

AU - on behalf of the MUST collaborators

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Introduction Acute peripheral arterial occlusions can be treated with intra-arterial catheter-directed thrombolysis as an alternative to surgical thromboembolectomy. Although less invasive, this treatment is time-consuming and carries a significant risk of haemorrhagic complications. Contrast-enhanced ultrasound using microbubbles could accelerate dissolution of thrombi by thrombolytic medications due to mechanical effects caused by oscillation; this could allow for lower dosages of thrombolytics and faster thrombolysis, thereby reducing the risk of haemorrhagic complications. In this study, the safety and practical applicability of this treatment will be investigated. Methods and analysis A single-arm phase II trial will be performed in 20 patients with acute peripheral arterial occlusions eligible for thrombolytic treatment. Low-dose catheter-directed thrombolysis with urokinase will be used. The investigated treatment will be performed during the first hour of thrombolysis, consisting of intravenous infusion of 4 Luminity phials (6 mL in total, diluted with saline 0.9% to 40 mL total) of microbubbles with the use of local ultrasound at the site of occlusion. Primary end points are the incidence of complications and technical feasibility. Secondary end points are angiographic and clinical success, duration of thrombolytic infusion, treatment-related mortality, amputations, additional interventions and quality of life. Ethics and dissemination Ethical approval for this study was obtained in 2015 from the Medical Ethics Committee of the VU University Medical Center, Amsterdam, the Netherlands. A statement of consent for this study was given by the Dutch national competent authority. Data will be presented at national and international conferences and published in a peer-reviewed journal. Trial registration numbers Dutch National Trial Registry: NTR4731; European Clinical Trials Database of the European Medicines Agency: 2014-003469-10; Pre-results.

AB - Introduction Acute peripheral arterial occlusions can be treated with intra-arterial catheter-directed thrombolysis as an alternative to surgical thromboembolectomy. Although less invasive, this treatment is time-consuming and carries a significant risk of haemorrhagic complications. Contrast-enhanced ultrasound using microbubbles could accelerate dissolution of thrombi by thrombolytic medications due to mechanical effects caused by oscillation; this could allow for lower dosages of thrombolytics and faster thrombolysis, thereby reducing the risk of haemorrhagic complications. In this study, the safety and practical applicability of this treatment will be investigated. Methods and analysis A single-arm phase II trial will be performed in 20 patients with acute peripheral arterial occlusions eligible for thrombolytic treatment. Low-dose catheter-directed thrombolysis with urokinase will be used. The investigated treatment will be performed during the first hour of thrombolysis, consisting of intravenous infusion of 4 Luminity phials (6 mL in total, diluted with saline 0.9% to 40 mL total) of microbubbles with the use of local ultrasound at the site of occlusion. Primary end points are the incidence of complications and technical feasibility. Secondary end points are angiographic and clinical success, duration of thrombolytic infusion, treatment-related mortality, amputations, additional interventions and quality of life. Ethics and dissemination Ethical approval for this study was obtained in 2015 from the Medical Ethics Committee of the VU University Medical Center, Amsterdam, the Netherlands. A statement of consent for this study was given by the Dutch national competent authority. Data will be presented at national and international conferences and published in a peer-reviewed journal. Trial registration numbers Dutch National Trial Registry: NTR4731; European Clinical Trials Database of the European Medicines Agency: 2014-003469-10; Pre-results.

KW - microbubbles

KW - peripheral arterial occlusion

KW - sonothrombolysis

KW - thrombolysis

KW - ultrasound

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U2 - 10.1136/bmjopen-2016-014365

DO - 10.1136/bmjopen-2016-014365

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JF - BMJ Open

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