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CORRECTION article

Front. Neurol., 23 September 2024
Sec. Stroke
Volume 15 - 2024 | https://doi.org/10.3389/fneur.2024.1481563

Corrigendum: Direct oral anticoagulants for the treatment of cerebral venous thrombosis – a protocol of an international phase IV study

This article is a correction to:

  1. Direct oral anticoagulants for the treatment of cerebral venous thrombosis – a protocol of an international phase IV study

    1. Read original article
\r\nAnita van de Munckhof&#x;Anita van de Munckhof1†Mayte Snchez van Kammen&#x;Mayte Sánchez van Kammen1†Katarzyna KrzywickaKatarzyna Krzywicka1Sanjith AaronSanjith Aaron2Diana Aguiar de SousaDiana Aguiar de Sousa3Florina AntochiFlorina Antochi4Antonio ArauzAntonio Arauz5Miguel A. BarbozaMiguel A. Barboza6Adriana B. ConfortoAdriana B. Conforto7Francesco DentaliFrancesco Dentali8Daniel Galdames ContrerasDaniel Galdames Contreras9Xunming JiXunming Ji10Katarina Jood,Katarina Jood11,12Mirjam R. HeldnerMirjam R. Heldner13María Hernndez-PrezMaría Hernández-Pérez14Wayneho KamWayneho Kam15Timothy J. KleinigTimothy J. Kleinig16Espen S. KristoffersenEspen S. Kristoffersen17Ronen R. LekerRonen R. Leker18Robin LemmensRobin Lemmens19Sven PoliSven Poli20Nilüfer YeilotNilüfer Yeşilot21Mohammad WasayMohammad Wasay22Teddy Y. WuTeddy Y. Wu23Marcel ArnoldMarcel Arnold13Lia Lucas-NetoLia Lucas-Neto24Saskia MiddeldorpSaskia Middeldorp25Jukka PutaalaJukka Putaala26Turgut Tatlisumak,Turgut Tatlisumak11,12Jos M. FerroJosé M. Ferro27Jonathan M. Coutinho Jonathan M. Coutinho1* on behalf of the DOAC-CVT Study Group
  • 1Department of Neurology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands
  • 2Department of Neurology, Christian Medical College, Vellore, India
  • 3Department of Neurology, Stroke Center, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
  • 4Department of Neurology, Spitalul Universitar de Urgentă Bucureşti, Bucharest, Romania
  • 5Department of Neurology, National Institute of Neurology and Neurosurgery, Mexico City, Mexico
  • 6Department of Neurology, Rafael Angel Calderon Guardia Hospital, San José, Costa Rica
  • 7Department of Neurology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
  • 8Department of Neurology, Asst Sette Laghi, Varese, Italy
  • 9Stroke Unit, Hospital Clínico de la Universidad de Chile, Santiago, Chile
  • 10Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
  • 11Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden
  • 12Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
  • 13Department of Neurology, Inselspital, University Hospital and University of Bern, Bern, Switzerland
  • 14Department of Neurology, Hospital Germans Trias i Pujol, Badalona, Spain
  • 15Department of Neurology, Duke University Hospital, Durham, NC, United States
  • 16Department of Neurology, Royal Adelaide Hospital, Adelaide, SA, Australia
  • 17Department of Neurology, Akershus University Hospital, Nordbyhagen, Norway
  • 18Department of Neurology, Hadassah – Hebrew University Medical Center, Jerusalem, Israel
  • 19Department of Neurology, UZ Leuven, Leuven, Belgium
  • 20Department of Neurology, Tübingen University Hospital, Tübingen, Germany
  • 21Department of Neurology, Istanbul Tip Fakültesi, Istanbul, Turkey
  • 22Department of Neurology, Aga Khan University, Karachi, Pakistan
  • 23Department of Neurology, Christchurch Hospital, Christchurch, New Zealand
  • 24Department of Neuroradiology, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
  • 25Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
  • 26Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
  • 27Centro de Estudos Egas Moniz, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal

A corrigendum on
Direct oral anticoagulants for the treatment of cerebral venous thrombosis – a protocol of an international phase IV study

by van de Munckhof A, Sánchez van Kammen M, Krzywicka K, Aaron S, Aguiar de Sousa D, Antochi F, Arauz A, Barboza MA, Conforto AB, Dentali F, Galdames Contreras D, Ji X, Jood K, Heldner MR, Hernández-Pérez M, Kam W, Kleinig TJ, Kristoffersen ES, Leker RR, Lemmens R, Poli S, Yeşilot N, Wasay M, Wu TY, Arnold M, Lucas-Neto L, Middeldorp S, Putaala J, Tatlisumak T, Ferro JM and Coutinho JM (2023). Front. Neurol. 14:1251581. doi: 10.3389/fneur.2023.1251581

Two corrections have been made to the Statistical Analysis Plan as previously published in Section 2. Methods and analysis, subsection “2.7. Statistical analysis plan.” First, given the large number of participating centers and the expected low incidence of the primary endpoint, adjusting for center of inclusion in the outcome model is not considered feasible. Instead, we added country of inclusion's income group as classified by The World Bank (15) to the list of confounders, which will be used to model the propensity score.

Second, we will not use multiple imputation for missing outcome data, but only for missing data on confounders. Given that most events occur in the first period after diagnosis, (10) the last observation carried forward approach will be used if the 6- and 12-month follow-up data are missing. To assess the influence of this approach, we will perform an additional sensitivity analysis conducting a worst-case scenario approach i.e., using the assumption that all patients with missing outcome data would have suffered a primary endpoint event.

Additionally, for clarification, the on-treatment analysis as described in Section “2.7.2. Sensitivity analyses for the primary endpoint” will be descriptive only.

The DOAC-CVT Executive Committee decided on these changes on July 15, 2024, prior to closure of the database.

Section 2. Methods and analysis, subsection “2.7. Statistical analysis plan” will now read:

2.7. Statistical analysis plan

Analyses will be conducted according to the intention-to-treat principle. Patients will be grouped based on the first oral anticoagulant that was started (DOAC or VKA). Baseline characteristics will be presented for both groups (patients who were initially treated with DOACs and patients treated with VKAs). Counts and proportions will be provided for categorical data. Continuous data will be presented using means and standard deviations (SD) for normally distributed data and medians and interquartile ranges for non-normally distributed data. Any missing data on confounders will be imputed using multiple imputation.

2.7.1. Analysis of the primary endpoint

We will use propensity score inverse probability treatment weighting to calculate an adjusted odds ratio for the primary outcome. Based on the direct acyclic graph (Figure 1), the following confounders will be used to compute the propensity score:

• Age;

• Baseline renal function;

• Cancer (defined as currently under treatment or diagnosed within 6 months prior to CVT diagnosis);

• Central nervous system (CNS) infection concurrent with the index CVT;

• Concomitant antiplatelet use at start of oral anticoagulant treatment;

• Country of inclusion's income group as classified by The World Bank (15);

• Glasgow Coma Scale at hospital presentation;

• Intracranial hemorrhage (ICH) before start of oral anticoagulant treatment;

• Known antiphospholipid syndrome (APS), or presence of antiphospholipid antibodies at start of oral anticoagulant treatment;

• Previous major bleeding prior to the index CVT (according to ISTH criteria [Table 1]);

• Previous VTE.

We will analyze the balance of confounders between both treatment groups after propensity score inverse probability weighting. A last observation carried forward approach will be used if the 6- or 12-month follow-up data are missing.

2.7.2. Sensitivity analyses for the primary endpoint

In addition to the main analysis of the primary endpoint, we will perform four sensitivity analyses for the primary endpoint. Firstly, we will perform a survival analysis of the primary endpoint using the inverse probability weighting from the main analysis. Patients will be censored at the time of anticoagulant-switch or at the last follow-up moment (after 3, 6, or 12 months). Secondly, we will provide unadjusted analyses. Thirdly, we will repeat the analysis using a worst-case scenario approach i.e., using the assumption that all patients with missing outcome data have suffered a primary endpoint event. Lastly, we will perform a descriptive on-treatment analysis.

2.7.3. Secondary study outcomes

All secondary outcomes will be analyzed following the same methods as used for the primary endpoint. Confounders to be included in each propensity score calculation are detailed in Supplementary Figures 1–5.

2.7.4. Subgroup analysis

We will report all primary and secondary outcomes stratified by type of DOAC in an exploratory subgroup analysis if the number of cases is sufficient. In addition, we will perform a subgroup analysis for patients who were diagnosed with APS compared to patients who do not have APS. No formal statistical comparisons will be performed for these subgroup analyses.

The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Keywords: cerebral venous thrombosis, anticoagulants, DOAC, vitamin K antagonist, treatment

Citation: van de Munckhof A, Sánchez van Kammen M, Krzywicka K, Aaron S, Aguiar de Sousa D, Antochi F, Arauz A, Barboza MA, Conforto AB, Dentali F, Galdames Contreras D, Ji X, Jood K, Heldner MR, Hernández-Pérez M, Kam W, Kleinig TJ, Kristoffersen ES, Leker RR, Lemmens R, Poli S, Yeşilot N, Wasay M, Wu TY, Arnold M, Lucas-Neto L, Middeldorp S, Putaala J, Tatlisumak T, Ferro JM and Coutinho JM (2024) Corrigendum: Direct oral anticoagulants for the treatment of cerebral venous thrombosis – a protocol of an international phase IV study. Front. Neurol. 15:1481563. doi: 10.3389/fneur.2024.1481563

Received: 16 August 2024; Accepted: 29 August 2024;
Published: 23 September 2024.

Edited and reviewed by: Ken Butcher, University of Alberta, Canada

Copyright © 2024 van de Munckhof, Sánchez van Kammen, Krzywicka, Aaron, Aguiar de Sousa, Antochi, Arauz, Barboza, Conforto, Dentali, Galdames Contreras, Ji, Jood, Heldner, Hernández-Pérez, Kam, Kleinig, Kristoffersen, Leker, Lemmens, Poli, Yeşilot, Wasay, Wu, Arnold, Lucas-Neto, Middeldorp, Putaala, Tatlisumak, Ferro and Coutinho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Jonathan M. Coutinho, j.coutinho@amsterdamumc.nl

†These authors have contributed equally to this work and share first authorship

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.