CAVA (Ultrasound-accelerated catheter-directed thrombolysis on preventing post-thrombotic syndrome) trial: Long-term follow-up results

Pascale Notten; André A. E. A. de Smet; Lidwine W. Tick; Marlène H. W. van de Poel; Otmar R. M. Wikkeling; Louis-Jean Vleming; Ad Koster; Kon-Siong G. Jie; Esther M. G. Jacobs; Harm P. Ebben; Michiel Coppens; Hugo ten Cate; Cees H. A. Wittens; Arina J. ten Cate-Hoek

doi:10.1161/JAHA.120.018973

CAVA (Ultrasound-accelerated catheter-directed thrombolysis on preventing post-thrombotic syndrome) trial: Long-term follow-up results

Pascale Notten
, André A. E. A. de Smet
, Lidwine W. Tick
, Marlène H. W. van de Poel
, Otmar R. M. Wikkeling
, Louis-Jean Vleming
, Ad Koster
, Kon-Siong G. Jie
, Esther M. G. Jacobs
, Harm P. Ebben
, Michiel Coppens
, Hugo ten Cate
, Cees H. A. Wittens
, Arina J. ten Cate-Hoek^*

^*Corresponding author for this work

Maastricht University
Department of Medical Microbiology, Maasstad Hospital, Rotterdam, The Netherlands
Maxima Medical Centre
Department of Cardiology, Laurentius Hospital, Roermond, The Netherlands
Department of Cardiology, Nij Smellinghe Hospital, Drachten, The Netherlands
Haga Ziekenhuis
VieCuri Medisch Centrum
Zuyderland MC, Postbus 5500, 6130 MB, Sittard, The Netherlands;
Department of Obstetrics and Gynaecology, Helmond, Netherlands
University of Amsterdam
Emeritus professor of venous surgery, Amsterdam, the Netherlands
University of Limburg
Maastricht University Medical Center and Cardiovascular Research Institute Maastricht (CARIM)
Department of Cardiology, Maasstad Hospital, Rotterdam, the Netherlands
Laurentius Hospital
Nij Smellinghe Hospital
Department of Internal Medicine, Zuyderland Medical Centre, Sittard, the Netherlands
Elkerliek Hospital

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND: The CAVA (Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome) trial did not show a reduction of post-thrombotic syndrome (PTS) after additional ultrasound-accelerated catheter-directed thrombolysis in patients with acute iliofemoral deep vein thrombosis at 1-year follow-up. This prespecified analysis of the CAVA trial aimed to determine the impact of additional thrombolysis on outcomes of PTS at long-term follow-up. METHODS AND RESULTS: Patients aged 18 to 85 years with a first-time acute iliofemoral deep vein thrombosis were included and randomly assigned (1:1) to either standard treatment plus ultrasound-accelerated catheter-directed thrombolysis or standard treatment alone. The primary outcome was the proportion of PTS (Villalta score ≥5 on 2 occasions ≥3 months apart or venous ulceration) at the final follow-up visit. Additionally, PTS according to the International Society on Thrombosis and Haemostasis (ISTH) consensus definition was assessed to allow external comparability. Major bleedings were the main safety outcome. At a median follow-up of 39.0 months (interquartile range, 23.3–63.8), 120 patients (79.8%) participated in the final follow-up visit: 62 from the intervention group and 58 from the standard treatment group. PTS developed in 19 (30.6%) versus 26 (44.8%) patients, respectively (odds ratio [OR], 0.54; 95% CI, 0.26 to 1.15 [P=0.11]), with an absolute difference between groups of −14.2% (95% CI, −32.0% to 4.8%). Using the ISTH consensus definition, a significant reduction in PTS was observed (29 [46.8%] versus 40 [69.0%]) (OR, 0.40; 95% CI, 0.19–0.84 [P=0.01]) with an absolute difference between groups of −22.2% (95% CI, −39.8% to −2.8%). No new major bleedings occurred following the 12-month follow-up. CONCLUSIONS: The impact of additional ultrasound-accelerated catheter-directed thrombolysis on the prevention of PTS was found to increase with time. Although this study was limited by its sample size, the overall findings indicate a reduction of mild PTS without impact on quality of life.

Original language	English
Article number	e018973
Journal	Journal of the American Heart Association
Volume	10
Issue number	11
DOIs	https://doi.org/10.1161/JAHA.120.018973
Publication status	Published - 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Catheter-directed thrombolysis
Iliofemoral deep vein thrombosis
Long-term follow-up
Post-thrombotic syndrome
Quality of life

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Notten, P., de Smet, A. A. E. A., Tick, L. W., van de Poel, M. H. W., Wikkeling, O. R. M., Vleming, L.-J., Koster, A., Jie, K.-S. G., Jacobs, E. M. G., Ebben, H. P., Coppens, M., ten Cate, H., Wittens, C. H. A., & ten Cate-Hoek, A. J. (2021). CAVA (Ultrasound-accelerated catheter-directed thrombolysis on preventing post-thrombotic syndrome) trial: Long-term follow-up results. Journal of the American Heart Association, 10(11), Article e018973. https://doi.org/10.1161/JAHA.120.018973

@article{637745146caf44769fd7583aadd6e6ff,

title = "CAVA (Ultrasound-accelerated catheter-directed thrombolysis on preventing post-thrombotic syndrome) trial: Long-term follow-up results",

abstract = "BACKGROUND: The CAVA (Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome) trial did not show a reduction of post-thrombotic syndrome (PTS) after additional ultrasound-accelerated catheter-directed thrombolysis in patients with acute iliofemoral deep vein thrombosis at 1-year follow-up. This prespecified analysis of the CAVA trial aimed to determine the impact of additional thrombolysis on outcomes of PTS at long-term follow-up. METHODS AND RESULTS: Patients aged 18 to 85 years with a first-time acute iliofemoral deep vein thrombosis were included and randomly assigned (1:1) to either standard treatment plus ultrasound-accelerated catheter-directed thrombolysis or standard treatment alone. The primary outcome was the proportion of PTS (Villalta score ≥5 on 2 occasions ≥3 months apart or venous ulceration) at the final follow-up visit. Additionally, PTS according to the International Society on Thrombosis and Haemostasis (ISTH) consensus definition was assessed to allow external comparability. Major bleedings were the main safety outcome. At a median follow-up of 39.0 months (interquartile range, 23.3–63.8), 120 patients (79.8\%) participated in the final follow-up visit: 62 from the intervention group and 58 from the standard treatment group. PTS developed in 19 (30.6\%) versus 26 (44.8\%) patients, respectively (odds ratio [OR], 0.54; 95\% CI, 0.26 to 1.15 [P=0.11]), with an absolute difference between groups of −14.2\% (95\% CI, −32.0\% to 4.8\%). Using the ISTH consensus definition, a significant reduction in PTS was observed (29 [46.8\%] versus 40 [69.0\%]) (OR, 0.40; 95\% CI, 0.19–0.84 [P=0.01]) with an absolute difference between groups of −22.2\% (95\% CI, −39.8\% to −2.8\%). No new major bleedings occurred following the 12-month follow-up. CONCLUSIONS: The impact of additional ultrasound-accelerated catheter-directed thrombolysis on the prevention of PTS was found to increase with time. Although this study was limited by its sample size, the overall findings indicate a reduction of mild PTS without impact on quality of life.",

keywords = "Catheter-directed thrombolysis, Iliofemoral deep vein thrombosis, Long-term follow-up, Post-thrombotic syndrome, Quality of life",

author = "Pascale Notten and \{de Smet\}, \{Andr{\'e} A. E. A.\} and Tick, \{Lidwine W.\} and \{van de Poel\}, \{Marl{\`e}ne H. W.\} and Wikkeling, \{Otmar R. M.\} and Louis-Jean Vleming and Ad Koster and Jie, \{Kon-Siong G.\} and Jacobs, \{Esther M. G.\} and Ebben, \{Harm P.\} and Michiel Coppens and \{ten Cate\}, Hugo and Wittens, \{Cees H. A.\} and \{ten Cate-Hoek\}, \{Arina J.\}",

note = "Funding Information: The CAVA trial was originally funded by a grant from ZonMw (The Netherlands Organisation for Health Research and Development, project number 171101001) and additional funding was provided by the board of the Maastricht University Medical Centre. The funders of this study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. Funding Information: Dr Coppens reports grants and personal fees from Bayer Daiichi Sankyo, CSL Behring; grants from Boehringer Ingelheim, Pfizer, Bristol-Meyers Squibb, and Sanquin Blood Supply; and personal fees from Sobi, NovoNordisk, and UniQure, outside the submitted work. Dr ten Cate reports personal fees and other from Bayer; other from Pfizer and Coagulation profile; and personal fees from LEO Pharma, Gideon Pharmaceuticals, and Alveron Pharma, outside the submitted work. Dr Wittens reports grants from BTG International Group during the conduct of the study. None of the above-mentioned organizations had any involvement in the design, conduct, analysis, or report of the study data. The remaining authors have no disclosures to report. Funding Information: The CAVA trial was funded by a grant from ZonMw (The Netherlands Organisation for Health Research and Development, project number 171101001) and additional funding was provided by the board of the Maastricht University Medical Centre. The funders of this study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The authors involved in analyzing the data (P.N. and A.t.C.H.) had full access to all of the data in the study. The corresponding author had final responsibility for the decision to submit for publication. Publisher Copyright: {\textcopyright} 2021 The Authors.",

year = "2021",

doi = "10.1161/JAHA.120.018973",

language = "English",

volume = "10",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "American Heart Association Inc.",

number = "11",

}

Notten, P, de Smet, AAEA, Tick, LW, van de Poel, MHW, Wikkeling, ORM, Vleming, L-J, Koster, A, Jie, K-SG, Jacobs, EMG, Ebben, HP , Coppens, M, ten Cate, H, Wittens, CHA & ten Cate-Hoek, AJ 2021, 'CAVA (Ultrasound-accelerated catheter-directed thrombolysis on preventing post-thrombotic syndrome) trial: Long-term follow-up results', Journal of the American Heart Association, vol. 10, no. 11, e018973. https://doi.org/10.1161/JAHA.120.018973

TY - JOUR

T1 - CAVA (Ultrasound-accelerated catheter-directed thrombolysis on preventing post-thrombotic syndrome) trial: Long-term follow-up results

AU - Notten, Pascale

AU - de Smet, André A. E. A.

AU - Tick, Lidwine W.

AU - van de Poel, Marlène H. W.

AU - Wikkeling, Otmar R. M.

AU - Vleming, Louis-Jean

AU - Koster, Ad

AU - Jie, Kon-Siong G.

AU - Jacobs, Esther M. G.

AU - Ebben, Harm P.

AU - Coppens, Michiel

AU - ten Cate, Hugo

AU - Wittens, Cees H. A.

AU - ten Cate-Hoek, Arina J.

N1 - Funding Information: The CAVA trial was originally funded by a grant from ZonMw (The Netherlands Organisation for Health Research and Development, project number 171101001) and additional funding was provided by the board of the Maastricht University Medical Centre. The funders of this study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. Funding Information: Dr Coppens reports grants and personal fees from Bayer Daiichi Sankyo, CSL Behring; grants from Boehringer Ingelheim, Pfizer, Bristol-Meyers Squibb, and Sanquin Blood Supply; and personal fees from Sobi, NovoNordisk, and UniQure, outside the submitted work. Dr ten Cate reports personal fees and other from Bayer; other from Pfizer and Coagulation profile; and personal fees from LEO Pharma, Gideon Pharmaceuticals, and Alveron Pharma, outside the submitted work. Dr Wittens reports grants from BTG International Group during the conduct of the study. None of the above-mentioned organizations had any involvement in the design, conduct, analysis, or report of the study data. The remaining authors have no disclosures to report. Funding Information: The CAVA trial was funded by a grant from ZonMw (The Netherlands Organisation for Health Research and Development, project number 171101001) and additional funding was provided by the board of the Maastricht University Medical Centre. The funders of this study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The authors involved in analyzing the data (P.N. and A.t.C.H.) had full access to all of the data in the study. The corresponding author had final responsibility for the decision to submit for publication. Publisher Copyright: © 2021 The Authors.

PY - 2021

Y1 - 2021

N2 - BACKGROUND: The CAVA (Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome) trial did not show a reduction of post-thrombotic syndrome (PTS) after additional ultrasound-accelerated catheter-directed thrombolysis in patients with acute iliofemoral deep vein thrombosis at 1-year follow-up. This prespecified analysis of the CAVA trial aimed to determine the impact of additional thrombolysis on outcomes of PTS at long-term follow-up. METHODS AND RESULTS: Patients aged 18 to 85 years with a first-time acute iliofemoral deep vein thrombosis were included and randomly assigned (1:1) to either standard treatment plus ultrasound-accelerated catheter-directed thrombolysis or standard treatment alone. The primary outcome was the proportion of PTS (Villalta score ≥5 on 2 occasions ≥3 months apart or venous ulceration) at the final follow-up visit. Additionally, PTS according to the International Society on Thrombosis and Haemostasis (ISTH) consensus definition was assessed to allow external comparability. Major bleedings were the main safety outcome. At a median follow-up of 39.0 months (interquartile range, 23.3–63.8), 120 patients (79.8%) participated in the final follow-up visit: 62 from the intervention group and 58 from the standard treatment group. PTS developed in 19 (30.6%) versus 26 (44.8%) patients, respectively (odds ratio [OR], 0.54; 95% CI, 0.26 to 1.15 [P=0.11]), with an absolute difference between groups of −14.2% (95% CI, −32.0% to 4.8%). Using the ISTH consensus definition, a significant reduction in PTS was observed (29 [46.8%] versus 40 [69.0%]) (OR, 0.40; 95% CI, 0.19–0.84 [P=0.01]) with an absolute difference between groups of −22.2% (95% CI, −39.8% to −2.8%). No new major bleedings occurred following the 12-month follow-up. CONCLUSIONS: The impact of additional ultrasound-accelerated catheter-directed thrombolysis on the prevention of PTS was found to increase with time. Although this study was limited by its sample size, the overall findings indicate a reduction of mild PTS without impact on quality of life.

AB - BACKGROUND: The CAVA (Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome) trial did not show a reduction of post-thrombotic syndrome (PTS) after additional ultrasound-accelerated catheter-directed thrombolysis in patients with acute iliofemoral deep vein thrombosis at 1-year follow-up. This prespecified analysis of the CAVA trial aimed to determine the impact of additional thrombolysis on outcomes of PTS at long-term follow-up. METHODS AND RESULTS: Patients aged 18 to 85 years with a first-time acute iliofemoral deep vein thrombosis were included and randomly assigned (1:1) to either standard treatment plus ultrasound-accelerated catheter-directed thrombolysis or standard treatment alone. The primary outcome was the proportion of PTS (Villalta score ≥5 on 2 occasions ≥3 months apart or venous ulceration) at the final follow-up visit. Additionally, PTS according to the International Society on Thrombosis and Haemostasis (ISTH) consensus definition was assessed to allow external comparability. Major bleedings were the main safety outcome. At a median follow-up of 39.0 months (interquartile range, 23.3–63.8), 120 patients (79.8%) participated in the final follow-up visit: 62 from the intervention group and 58 from the standard treatment group. PTS developed in 19 (30.6%) versus 26 (44.8%) patients, respectively (odds ratio [OR], 0.54; 95% CI, 0.26 to 1.15 [P=0.11]), with an absolute difference between groups of −14.2% (95% CI, −32.0% to 4.8%). Using the ISTH consensus definition, a significant reduction in PTS was observed (29 [46.8%] versus 40 [69.0%]) (OR, 0.40; 95% CI, 0.19–0.84 [P=0.01]) with an absolute difference between groups of −22.2% (95% CI, −39.8% to −2.8%). No new major bleedings occurred following the 12-month follow-up. CONCLUSIONS: The impact of additional ultrasound-accelerated catheter-directed thrombolysis on the prevention of PTS was found to increase with time. Although this study was limited by its sample size, the overall findings indicate a reduction of mild PTS without impact on quality of life.

KW - Catheter-directed thrombolysis

KW - Iliofemoral deep vein thrombosis

KW - Long-term follow-up

KW - Post-thrombotic syndrome

KW - Quality of life

UR - https://www.scopus.com/pages/publications/85107390569

U2 - 10.1161/JAHA.120.018973

DO - 10.1161/JAHA.120.018973

M3 - Article

C2 - 34032127

SN - 2047-9980

VL - 10

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 11

M1 - e018973

ER -

CAVA (Ultrasound-accelerated catheter-directed thrombolysis on preventing post-thrombotic syndrome) trial: Long-term follow-up results

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Keywords

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