Tranexamic acid to prevent operation in chronic subdural haematoma (TORCH): study protocol for a randomised placebo-controlled clinical trial

BACKGROUND: Chronic subdural haematoma (cSDH) occurs mainly in the elderly. Surgical evacuation is effective, but in these old, often frail, patients with multi-comorbidity, surgery carries significant risks for future cognitive functioning and loss of independency. Therefore, a growing interest is noted for a non-surgical treatment with medication such as tranexamic acid (TXA). In five small retrospective series, this antifibrinolytic drug showed a beneficial effect on the spontaneous resolution of the haematoma, and with that, the necessity for surgery. METHODS: For this randomised, placebo-controlled clinical multicentre trial, all cSDH patients, over 50 years old with mild symptoms (Glasgow Coma Score (GCS) ≥ 14, modified National Institutes of Health Stroke Scale (mNIHSS) ≤ 4), a midline shift of ≤ 10 mm and in whom a primary conservative treatment is chosen, are eligible for study participation. After informed consent, 140 patients will be randomised to receive either TXA 500 mg or placebo two times daily for 28 days. The primary outcome is the necessity for surgery within 12 weeks; secondary outcomes are cSDH volume, neurological impairment (mNIHSS), falling incidents, cognitive functioning (Montreal Cognitive Assessment (MOCA)), performance in activities of daily living (Barthel and Lawton score), functional outcome (modified Rankin Scale (mRS)), quality of life (Short Form Health Survey (SF-36) and EuroQol 5-Dimension Health Survey (EQ-5D)), mortality and the use of care and health-related costs (Medical Consumption Questionnaire (iMCQ) and Productivity Cost Questionnaire (iPCQ)) at 12 weeks and 6 months. DISCUSSION: This phase III trial investigating the efficacy of TXA to prevent surgery for cSDH is the first in including patients using anticoagulants and mentally incompetent patients, since these comprise a significant part of the target population. Also, this study is one of the first to prospectively measure functional outcome and quality of life in cSDH patients. Final results of this study are expected in 2024. TRIAL REGISTRATION: Dutch Trial Registry (Nederlands Trial Register) NL6584. Registered on 11 November 2017 ClinicalTrials.govNCT03582293. Registered on 11 July 2018 EU Clinical Trials Register 2017-004311-40. Registered on 29 March 201

Tranexamic acid to prevent operation in chronic subdural haematoma (TORCH): study protocol for a randomised placebo-controlled clinical trial

Background: Chronic subdural haematoma (cSDH) occurs mainly in the elderly. Surgical evacuation is effective, but in these old, often frail, patients with multi-comorbidity, surgery carries significant risks for future cognitive functioning and loss of independency. Therefore, a growing interest is noted for a non-surgical treatment with medication such as tranexamic acid (TXA). In five small retrospective series, this antifibrinolytic drug showed a beneficial effect on the spontaneous resolution of the haematoma, and with that, the necessity for surgery. Methods: For this randomised, placebo-controlled clinical multicentre trial, all cSDH patients, over 50 years old with mild symptoms (Glasgow Coma Score (GCS) ≥ 14, modified National Institutes of Health Stroke Scale (mNIHSS) ≤ 4), a midline shift of ≤ 10 mm and in whom a primary conservative treatment is chosen, are eligible for study participation. After informed consent, 140 patients will be randomised to receive either TXA 500 mg or placebo two times daily for 28 days. The primary outcome is the necessity for surgery within 12 weeks; secondary outcomes are cSDH volume, neurological impairment (mNIHSS), falling incidents, cognitive functioning (Montreal Cognitive Assessment (MOCA)), performance in activities of daily living (Barthel and Lawton score), functional outcome (modified Rankin Scale (mRS)), quality of life (Short Form Health Survey (SF-36) and EuroQol 5-Dimension Health Survey (EQ-5D)), mortality and the use of care and health-related costs (Medical Consumption Questionnaire (iMCQ) and Productivity Cost Questionnaire (iPCQ)) at 12 weeks and 6 months. Discussion: This phase III trial investigating the efficacy of TXA to prevent surgery for cSDH is the first in including patients using anticoagulants and mentally incompetent patients, since these comprise a significant part of the target population. Also, this study is one of the first to prospectively measure functional outcome and quality of life in cSDH patients. Final results of this study are expected in 2024. Trial registration: Dutch Trial Registry (Nederlands Trial Register) NL6584. Registered on 11 November 2017 ClinicalTrials.govNCT03582293. Registered on 11 July 2018 EU Clinical Trials Register 2017-004311-40. Registered on 29 March 201

Tranexamic acid to prevent operation in chronic subdural haematoma (TORCH): study protocol for a randomised placebo-controlled clinical trial

Background: Chronic subdural haematoma (cSDH) occurs mainly in the elderly. Surgical evacuation is effective, but in these old, often frail, patients with multi-comorbidity, surgery carries significant risks for future cognitive functioning and loss of independency. Therefore, a growing interest is noted for a non-surgical treatment with medication such as tranexamic acid (TXA). In five small retrospective series, this antifibrinolytic drug showed a beneficial effect on the spontaneous resolution of the haematoma, and with that, the necessity for surgery. Methods: For this randomised, placebo-controlled clinical multicentre trial, all cSDH patients, over 50 years old with mild symptoms (Glasgow Coma Score (GCS) ≥ 14, modified National Institutes of Health Stroke Scale (mNIHSS) ≤ 4), a midline shift of ≤ 10 mm and in whom a primary conservative treatment is chosen, are eligible for study participation. After informed consent, 140 patients will be randomised to receive either TXA 500 mg or placebo two times daily for 28 days. The primary outcome is the necessity for surgery within 12 weeks; secondary outcomes are cSDH volume, neurological impairment (mNIHSS), falling incidents, cognitive functioning (Montreal Cognitive Assessment (MOCA)), performance in activities of daily living (Barthel and Lawton score), functional outcome (modified Rankin Scale (mRS)), quality of life (Short Form Health Survey (SF-36) and EuroQol 5-Dimension Health Survey (EQ-5D)), mortality and the use of care and health-related costs (Medical Consumption Questionnaire (iMCQ) and Productivity Cost Questionnaire (iPCQ)) at 12 weeks and 6 months. Discussion: This phase III trial investigating the efficacy of TXA to prevent surgery for cSDH is the first in including patients using anticoagulants and mentally incompetent patients, since these comprise a significant part of the target population. Also, this study is one of the first to prospectively measure functional outcome and quality of life in cSDH patients. Final results of this study are expected in 2024. Trial registration: Dutch Trial Registry (Nederlands Trial Register) NL6584. Registered on 11 November 2017 ClinicalTrials.govNCT03582293. Registered on 11 July 2018 EU Clinical Trials Register 2017-004311-40. Registered on 29 March 201

Competing Ways Towards International Antitrust: The WTO versus the ICN

In times of globalization, trade liberalization and deregulation of specific industries, competition authorities face new challenges in order to protect national as well as international competition. With companies operating in various countries, fading market frontiers and increasing crossborder trade, new strategies must be developed in order to overcome threats to domestic markets resulting of anticompetitive behavior abroad. Even though solutions such as the Effects Doctrine or bilateral agreements allow albeit imperfectly countries to protect their domestic market, there are no laws safeguarding the global economy and international competition. Thus, the request arises to establish an international competition policy regime in order to harmonize countries competition laws, to reduce conflicts due to cross-border anti-competitive behavior and to support developing countries in reaching Western standards. Among several approaches, two are of significant interest: On the one hand, the World Trade Organization (WTO) could be enhanced by a board of supervision for international competition issues including a harmonized competition code for all, while on the other hand the International Competition Network (ICN) has been established to take care of global competition concerns through policy coordination [Graham 2003; Janow 2003; Budzinski 2004b]. This paper discusses whether the institutional WTO or the voluntary ICN approach represents the better path to an international competition policy regime to control private anticompetitive activities. The second part will explain the importance of an international competition policy. Subsequently, unilateral, bilateral and multilateral approaches to the prevention and solution of problems in global competition are introduced. Section 3.1 gives a short overview of the WTOs characteristics, its structural organization and its plans to integrate an international competition policy. The organization and the framework of the ICN as well as its attempts to prevent international anticompetitive behavior is explored in section 3.2. Based on the statements made in section 2 and the facts presented in section 3, the fourth section compares the WTO approach with the ICN qualities. The discussion will be divided into the following six criteria: (i) feasibility, (ii) acceptability, (iii) efficiency, (iv) negotiation and implementation of international competition rules, (v) conflict resolution and (vi) adaptability. Conclusions follow in section 5