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Tranexamic Acid in Chronic Subdural Hematomas (TRACS): study protocol for a randomized controlled trial.

ABSTRACT: Chronic subdural hematoma (CSDH) is one of the most frequent reason for cranial neurosurgical consultation. There is no widely accepted medical treatment for this condition. Herein, we present the protocol for the Tranexamic Acid (TXA) in Chronic Subdural Hematomas (TRACS) trial aiming at determining whether TXA can increase the rate of CSDH resolution following conservative management, lower the number of required surgical procedures and decrease the rate of CSDH recurrence following surgical evacuation.TRACS is a multicenter, double-blind, randomized, parallel-design, placebo-controlled, phase IIB study designed to provide preliminary efficacy data as well as feasibility, safety and incidence data required to plan a larger definitive phase III trial. Consecutive patients presenting with a diagnosis of chronic subdural hematoma will be screened for eligibility. Exclusion criteria include: specific risk factors for thromboembolic disease, anticoagulant use or contraindication to TXA. A total of 130 patients will be randomized to receive either 750 mg of TXA daily or placebo until complete radiological resolution of the CSDH or for a maximum of 20 weeks. CSDH volume will be measured on serial computed tomography (CT) scanning. Cognitive function tests, quality of life questionnaires as well as functional autonomy assessments will be performed at enrollment, at 10 weeks following randomization and at 3 months following treatment cessation. During the treatment period, patients will undergo standard CSDH management with surgery being performed at the discretion of the treating physician. If surgery is performed, the CSDH and its outer membrane will be sampled for in vitro analysis. The primary outcome is the rate of CSDH resolution by 20 weeks without intervening unplanned surgical procedure. Secondary outcomes include: CSDH volume, incidence of surgical evacuation procedures, CSDH recurrence, cognitive functions, functional autonomy, quality of life, incidence of complications and length of hospital stay. Planned subgroup analyses will be performed for conservatively versus surgically managed subjects and highly versus poorly vascularized CSDH.CSDH is a frequent morbidity for which an effective medical treatment has yet to be discovered. The TRACS trial will be the first prospective study of TXA for CSDH.NCT ID: NCT02568124 .

SUBMITTER: Iorio-Morin C

PROVIDER: S-EPMC4857422 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Tranexamic Acid in Chronic Subdural Hematomas (TRACS): study protocol for a randomized controlled trial.

Iorio-Morin Christian C Blanchard Jocelyn J Richer Maxime M Mathieu David D

Trials 20160505 1

<h4>Background</h4>Chronic subdural hematoma (CSDH) is one of the most frequent reason for cranial neurosurgical consultation. There is no widely accepted medical treatment for this condition. Herein, we present the protocol for the Tranexamic Acid (TXA) in Chronic Subdural Hematomas (TRACS) trial aiming at determining whether TXA can increase the rate of CSDH resolution following conservative management, lower the number of required surgical procedures and decrease the rate of CSDH recurrence f ...[more]

PMID: 27150916

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Project description:BackgroundChronic 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.MethodsFor 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.DiscussionThis 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 registrationDutch Trial Registry (Nederlands Trial Register) NL6584 . Registered on 11 November 2017 ClinicalTrials.gov NCT03582293 . Registered on 11 July 2018 EU Clinical Trials Register 2017-004311-40 . Registered on 29 March 2018.

Project description:Chronic subdural hematoma (CSDH) is a common disease that is more prevalent in older people. Surgical intervention is a safe treatment of choice. However, the recurrence rate is relatively high and the outcome is not always satisfactory among surgically treated patients. It is believed that aberrant angiogenesis and intracapsular inflammation contribute to the development of CSDH. Atorvastatin is reported to promote angiogenesis and suppress inflammation. We have recently shown that atorvastatin is effective to non-surgically reduce and eliminate CSDH with minimal side effects. Here, we report a clinical research trial protocol that is designed to evaluate the therapeutic effects of atorvastatin on CSDH.We have designed a multi-center, randomized, placebo-controlled, double blind clinical trial for evaluating the efficacy of oral atorvastatin in reducing CSDH. We have so far recruited 96 patients with CT-confirmed or MRI-confirmed CSDHs from 16 medical centers in China. These patients were originally recruited for the Oriental Neurosurgical Evidence-based Study Team (ONET) study. After informed consent is provided, patients are randomized to receive either atorvastatin (oral 20 mg/night for 8 weeks) or placebo (dextrin for 8 weeks); and followed for 16 weeks after the treatment. The primary outcome is the change in hematoma volume at the end of 8-week treatment. Secondary outcomes include: changes in 1) the hematoma volume at the 4(th), 12(th), and 24(th) weeks; 2) Markwalder's Grading Scale and Glasgow Coma Scale (MGS-GCS); 3) Glasgow Outcome Score (GOS) and 4) Activities of Daily Life-the Barthel Index scale (ADL-BI). Safety will be assessed during the study by monitoring adverse events, laboratory tests, electrocardiography (ECG), measurements of vital signs (temperature, pulse, and blood pressure) and body weight.Results of this trial will provide critical information regarding whether atorvastatin is an effective and safe alternative to surgical treatment of CSDH.ClinicalTrials.gov Identifier--NCT02024373 The date of trial registration: 7 August 2013.

Project description:BACKGROUND:Evidence increases that a high or a standard dose of tranexamic acid (TA) reduces postpartum bleeding. The TRACES pharmacobiological substudy aims to establish a therapeutic strategy in hemorrhagic (H) Cesarean section (CS) with respect to the intensity of fibrinolysis by using innovative assays. METHOD/DESIGN:The TRACES trial is a multicenter, randomized, double-blind, placebo-controlled, TA dose-ranging study that measures simultaneously plasmatic and uterine and urine TA concentrations and the plasmin peak inhibition tested by a simultaneous thrombin plasmin generation assay described by Van Geffen (novel hemostasis assay [NHA]). Patients undergoing H CS (>800 mL) will receive blindly TA 0.5 g or 1 g or placebo. A non-hemorrhagic (NH) group will be recruited to establish plasmin generation profile. Venous blood will be sampled before, at the end, and then at 30, 60, 120, and 360 min after injection. Uterine bleeding will be sampled after injection. Urine will be sampled 2 h and 6 h after injection. The number of patients entered into the study will be 114 H + 48 NH out of the 390 patients of the TRACES clinical trial. DISCUSSION:To explore the two innovative assays, a preliminary pilot study was conducted. Blood samples were performed repeatedly in patients undergoing either a H (>800 mL) or NH (<800 mL) CS and in non-pregnant women (NP). H patients received TA (0-2 g). Dose-dependent TA plasmatic concentrations were determined by LC-MS/MS quantification. Plasmin generation and its inhibition were tested in vitro and in vivo using the simultaneous thrombin-plasmin generation assay (STPGA). The pilot study included 15 patients in the H group, ten patients in the NH group, and seven patients in the NP group. TA plasmatic concentration showed a dose-dependent variation. STPGA inter-assay variation coefficients were < 20% for all plasmin parameters. Inter-individual dispersion of plasmin generation capacity was higher in H and NH groups than in NP group. Profile evolution over time was different between groups. This preliminary technical validation study allows TRACES pharmacobiological trial to be conducted. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02797119. Registered on 13 June 2016.

Project description:Background: The possible influence of different antithrombotic drugs on outcome after neurosurgical treatment of chronic subdural hematoma (CSDH) is still unclear. Nowadays, no randomized clinical trials are available. A metanalysis including 24 studies for a total of 1,812 pooled patients concluded that antiplatelets and anticoagulations present higher risk of recurrences. On the other hand, several studies highlighted that antithrombotic suspension, timing of surgery, and resumption of these drugs are still debated, and patients taking these present higher risk of thromboembolic events with no excess risk of bleed recurrences or worse functional outcome. Our assumption is that the real hemorrhagic risk related to antithrombotic drug continuation in CSDH may be overrated and the thromboembolic risk for discontinuation underestimated, especially in patients with high cardiovascular risk. Methods: A comprehensive literature review with the search terms "acetylsalicylic acid" and "chronic subdural x" was performed. Clinical status, treatment, time of drug discontinuation, complications (in particular, rebleeding or thromboembolic events), and clinical and radiological outcome at follow-up were evaluated. Results: Five retrospective studies were selected for the review, three of them reporting specifically low-dose acetylsalicylic intake and two of them general antithrombotic drugs for a total of 1,226 patients. Only two papers reported the thromboembolic rate after surgery; in one paper, it is not even divided from other cardiac complications. Conclusion: The literature review does not clarify the best management of low-dose acetylsalicylic in CSDH patients, in particular, concerning the balance between thromboembolic event rates and rebleeding risks. We do believe that CSDH precipitates the worsening of comorbidities with a resulting increased mortality. Further studies clearly evaluating the thromboembolic events are strongly needed to clarify this topic. In this perspective paper, we discuss the difficult choice of low-dose acetylsalicylic acid (LDAA) management in patients suffering from chronic subdural hematoma (CSDH). The balance between hemorrhagic and thromboembolic risks often represents a sword of Damocles for neurosurgeons, especially when dealing with patients with high cardiovascular risk. No guidelines are currently available, and a survey by Kamenova et al. showed that most neurosurgeons discontinue LDAA treatment for at least 7 days in the perioperative period of surgical evacuation of CSDH, even though recent studies show that early LDAA resumption might be safe. Thrombosis prophylaxis is administered by only 60%, even though patients with CSDH are at high risk of developing thromboembolic complications. We would like to bring attention to this controversial issue.

Project description:Objective: This study aimed to evaluate the correlation between arachnoid cysts and chronic subdural hematomas in young adults. Methods: This retrospective study evaluated ten patients having concomitant chronic subdural hematomas and arachnoid cysts. Patients were evaluated with the data of age and gender, location of hematoma and arachnoid cyst, trauma history, symptoms at admission, maximum hematoma diameter, contiguity between arachnoid cyst and hematoma, and treatment methods. Results: We treated 285 patients who were diagnosed with cSDH between January 2013 and December 2019. 22 patients were under the age of 40 years. Ten of them had both cSDH and arachnoid cysts. The mean age of patients was 24.8±3.9 years. Patients with only chronic subdural hematoma had higher mean age than the patients with arachnoid cyst-related chronic subdural hematoma. In four patients, the onset of chronic subdural hematoma was reported after arachnoid cyst diagnosis. Four of the patients did not have causative trauma history, and two patients suffered minor sports-related traumas. All patients had headache, and only two patients had hemiparesis. The location of arachnoid cysts were in the middle fossa in eight patients. All patients had chronic subdural hematomas on the ipsilateral side of arachnoid cyst. Four patients who had smaller than 10 mm maximal cSDH diameter underwent conservative management. They were followed by serial neuroimaging studies and it was noted that the hematoma disappered and the size of the arachnoid cysts decreased over time without any neurological complication. In six cases, craniotomy was required, and all recovered completely. cSDH did not recur during 5-60 months of follow-up period (median 12 months). Conclusions: It seems that presence of an arachnoid cyst in young adults is a predisposing factor for the formation of chronic subdural hematoma. Coincidentally diagnosed arachnoid cyst patients may be followed up with periodical clinical examinations and neuroimaging studies.

Project description:BACKGROUND:Chronic subdural haematoma (CSDH) is a common neurological disease with a rapidly rising incidence due to increasing age and widespread use of anticoagulants. Surgical intervention by burr-hole craniotomy (BHC) is the current standard practice for symptomatic patients, but associated with complications, a recurrence rate of up to 30% and increased mortality. Dexamethasone (DXM) therapy is, therefore, used as a non-surgical alternative but considered to achieve a lower success rate. Furthermore, the benefit of DXM therapy appears much more deliberate than the immediate relief from BHC. Lack of evidence and clinical equipoise among caregivers prompts the need for a head-to-head randomised controlled trial. The objective of this study is to compare the effect of primary DXM therapy versus primary BHC on functional outcome and cost-effectiveness in symptomatic patients with CSDH. METHODS/DESIGN:This study is a prospective, multicentre, randomised controlled trial (RCT). Consecutive patients with a CSDH with a Markwalder Grading Scale (MGS) grade 1 to 3 will be randomised to treatment with DXM or BHC. The DXM treatment scheme will be 16 mg DXM per day (8 mg twice daily, days 1 to 4) which is then halved every 3 days until a dosage of 0.5 mg a day on day 19 and stopped on day 20. If the treatment response is insufficient (i.e. persistent or progressive symptomatology due to insufficient haematoma resolution), additional surgery can be performed. The primary outcomes are the functional outcome by means of the modified Rankin Scale (mRS) score at 3 months and cost-effectiveness at 12 months. Secondary outcomes are quality of life at 3 and 12 months using the Short Form Health Survey (SF-36) and Quality of Life after Brain Injury Overall Scale (QOLIBRI), haematoma thickness after 2 weeks on follow-up computed tomography (CT), haematoma recurrence during the first 12 months, complications and drug-related adverse events, failure of therapy within 12 months after randomisation and requiring intervention, mortality during the first 3 and 12 months, duration of hospital stay and overall healthcare and productivity costs. To test non-inferiority of DXM therapy compared to BHC, 210 patients in each treatment arm are required (assumed adjusted common odds ratio DXM compared to BHC 1.15, limit for inferiority <?0.9). The aim is to include a total of 420 patients in 3 years with an enrolment rate of 60%. DISCUSSION:The present study should demonstrate whether treatment with DXM is as effective as BHC on functional outcome, at lower costs. TRIAL REGISTRATION:EUCTR 2015-001563-39 . Date of registration: 29 March 2015.

Project description:BACKGROUND:An antifibrinolytic agent that blocks lysine-binding sites on plasminogen molecules, tranexamic acid reduces bleeding-related mortality in women with postpartum hemorrhage (PPH), especially administered fairly soon after delivery. According to the randomized controlled trials thus far reported for PPH prevention after cesarean deliveries (n?=?16), women who received tranexamic acid had significantly less postpartum blood loss and no increase in severe adverse effects. These were, however, primarily small single-center studies that had fundamental methodological flaws. Multicenter randomized controlled trials with adequate power are necessary to demonstrate its value persuasively before tranexamic acid goes into widespread use for the prevention of PPH after cesarean deliveries. METHODS/DESIGN:This study will be a multicenter, double-blind, randomized controlled trial with two parallel groups including 4524 women with cesarean deliveries before or during labor, at a term ?34?weeks, modeled on our previous study of tranexamic acid administered after vaginal deliveries. Treatment (either tranexamic acid 1?g or placebo) will be administered intravenously just after birth. All women will also receive a prophylactic uterotonic agent. The primary outcome will be the incidence of PPH, defined by a calculated estimated blood loss >?1000?mL or a red blood cell transfusion before day 2 postpartum. This study will have 80% power to show a 20% reduction in the incidence of PPH, from 15.0 to 12.0%. DISCUSSION:As an, inexpensive, easy to administer drug that can be add to the routine management of cesarean births in delivery rooms, tranexamic acid is a promising candidate for preventing PPH after these births. This large, adequately powered, multicenter randomized placebo-controlled trial seeks to determine if the benefits of the routine prophylactic use of tranexamic acid after cesarean delivery significantly outweigh its risks. TRIAL REGISTRATION:ClinicalTrials.gov NCT03431805 (February 12, 2018).

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Tranexamic Acid in Chronic Subdural Hematomas (TRACS): study protocol for a randomized controlled trial.

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Tranexamic Acid in Chronic Subdural Hematomas (TRACS): study protocol for a randomized controlled trial.

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