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Comparative Study of Combination of Oral Tranexamic Acid With Modified Kligman's Formula Versus Oral Tranexamic Acid With Azelaic Acid 15% in the Treatment of Melasma
Singh, R., Maheshwari, P., Madke, B., Singh, A., Jawade, S.
Cureus. 2023;15(6):e40908
Abstract
Background Melasma is a persistent skin condition affecting individuals of Asian, African, and Hispanic backgrounds. It causes dark patches on sun-exposed areas of the face. The exact causes are unclear, but UV light and hormonal factors play a role. Melasma significantly impacts physical appearance and quality of life, causing emotional and social distress. Objective The objective was to compare the efficacy of a combination of oral tranexamic acid and modified Kligman's formula vs. oral tranexamic acid and 15% azelaic acid. Material and methods This two-year interventional study occurred at the Outpatient Department of Dermatology, Venereology, and Leprosy in Sawangi, Maharashtra. It included male and female patients aged 18-50 with melasma seeking treatment. Ethical approval was obtained, and data collection involved medical histories, skin examinations, and calculating the Melasma Area and Severity Index (MASI). Results The study found no significant association between age groups and subject distribution in Groups A and B. Significant differences were observed in MASI scores within each group over time. There was a significant difference in mean MASI scores between Group A and Group B at the eight-week mark. A burning sensation was significantly associated with the groups, while no significant association was found for erythema. Conclusion This study concludes that combining oral tranexamic acid with a modified Kligman's formula is more effective in treating melasma than combining oral tranexamic acid with azelaic acid 15%.
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Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial
Polymeris, A. A., Karwacki, G. M., Siepen, B. M., Schaedelin, S., Tsakiris, D. A., Stippich, C., Guzman, R., Nickel, C. H., Sprigg, N., Kägi, G., et al
Stroke. 2023
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Abstract
BACKGROUND Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH. METHODS We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis. RESULTS Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P=0.40). There was a signal for interaction with onset-to-treatment time (P(interaction)=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P=0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P=0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation. CONCLUSIONS In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH. REGISTRATION URL: https://clinicaltrials.gov; Unique identifier: NCT02866838.
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Tranexamic Acid in Non-Traumatic Intracerebral Haemorrhage (TANICH II): Introducing the Potential Role of 3 g Tranexamic Acid in Haematoma Reduction
Arumugam, A., Tan, S. E., Tan, S. L., Tan, J. E., Hussin, F. H., Zenian, M. S., Idris, Z., Abdullah, J. M.
The Malaysian journal of medical sciences : MJMS. 2023;30(3):93-102
Abstract
BACKGROUND Intracerebral haemorrhage (ICH) can be devastating, particularly if haematoma expansion occurs. The efficacy of tranexamic acid (TXA), an anti-fibrinolytic agent, in reducing haematoma expansion is now being studied worldwide. However, the optimal dosage of TXA has yet to be determined. This study was designed to further establish the potential of different doses of TXA. METHODS A double-blinded, randomised, placebo-controlled study was carried out among adults with non-traumatic ICH. Eligible study subjects were randomly assigned to receive placebo, 2-g TXA treatment or 3-g TXA treatment. Haematoma volumes before and after intervention were measured using the planimetric method. RESULTS A total of 60 subjects with 20 subjects in each treatment group were recruited for this study. Among the 60 subjects, the majority were male (n = 36, 60%), had known cases of hypertension (n = 43, 71.7%) and presented with full Glasgow coma scale (GCS) (n = 41, 68.3%). The results showed that there was no statistically significant difference (P = 0.315) in the mean changes of haematoma volume when compared with three study groups using ANCOVA, although the 3-g TXA group was the only group that showed haematoma volume reduction (mean reduction of 0.2 cm(3)) instead of expansion as in placebo (mean expansion 1.8 cm(3)) and 2-g TXA (mean expansion 0.3 cm(3)) groups. Good recovery was observed in all study groups, with only three subjects being moderately disabled. No adverse effects were reported in any of the study groups. CONCLUSION To the best of our knowledge, this is the first clinical study using 3 g of TXA in the management of non-traumatic ICH. From our study, 3 g of TXA may potentially be helpful in reducing haematoma volume. Nonetheless, a larger-scale randomised controlled trial should be carried out to further establish the role of 3 g of TXA in non-traumatic ICH.
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Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post-Hoc Analysis of the ULTRA Trial
Tjerkstra MA, Post R, Germans MR, Vergouwen MDI, Jellema K, Koot RW, Kruyt ND, Willems PWA, Wolfs JFC, de Beer FC, et al
Neurology. 2022
Abstract
BACKGROUND AND OBJECTIVES The ULTRA-trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at six months. An expected proportion of the included patients had non-aneurysmal subarachnoid hemorrhage In this post-hoc study, we will investigate whether ultra-early and short-term tranexamic acid treatment in patients with aneurysmal subarachnoid hemorrhage improves clinical outcome at six months. METHODS The ULTRA-trial is a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment, conducted between July 24, 2013 and January 20, 2020. After confirmation of subarachnoid hemorrhage on non-contrast computer tomography, patients were allocated to either ultra-early and short-term tranexamic acid treatment with usual care, or usual care only. In this post-hoc analysis, we included all ULTRA-participants with a confirmed aneurysm on CT angiography and/or digital subtraction angiography. The primary endpoint was clinical outcome at six months, assessed by the modified Rankin Scale, dichotomized into good (0-3) and poor (4-6) outcome. RESULTS Of the 813 ULTRA-trial patients who had an aneurysmal subarachnoid hemorrhage, 409 (50%) were assigned to the tranexamic acid group and 404 (50%) to the control group. In the intention-to-treat analysis, 233 of 405 (58%) patients in the tranexamic acid group and 238 of 399 (60%) patients in the control group had a good clinical outcome (adjusted odds ratio (aOR) 0·92; 95% confidence interval (C.I.) 0·69 to 1·24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) aOR 0.76, 95% C.I. 0.57-1.03, all-cause mortality at 30 days aOR 0.91, 95% C.I. 0.65-1.28), all-cause mortality at six months aOR 1.10 (95% C.I. 0.80-1.52). DISCUSSION Ultra-early and short-term tranexamic acid treatment did not improve clinical outcome at six months in patients with aneurysmal subarachnoid hemorrhage and therefore, cannot be recommended. TRIAL REGISTRATION ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24(th), 2013). CLASSIFICATION OF EVIDENCE This study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.
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A Randomized Trial of Oral Tranexamic Acid With Fluocinolone-Based Triple Cream Versus Fluocinolone Based Triple Cream Alone for the Treatment of Melasma
Perveen, S., Rubin, A., Berger, L., Xiong, W., Waqas, N., Sharif, S., Rao, B.
Journal of Drugs in Dermatology : Jdd. 2022;21(3):321-322
Abstract
Oral tranexamic acid (TXA) is a relatively new treatment option for melasma. It is thought to reduce hyperpigmentation through inhibition of the plasminogen/plasmin pathway with resulting decreases in epidermal melanocyte tyrosinase activity, inflammatory mediators, dermal neovascularization, and mast cell numbers.
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Modulation of thromboinflammation in hospitalized COVID-19 patients with aprotinin, low molecular weight heparin, and anakinra: The DAWn-Antico study
Engelen MM, Van Thillo Q, Betrains A, Gyselinck I, Martens CP, Spalart V, Ockerman A, Devooght C, Wauters J, Gunst J, et al
Research and practice in thrombosis and haemostasis. 2022;6(7):e12826
Abstract
BACKGROUND Thromboinflammation plays a central role in severe COVID-19. The kallikrein pathway activates both inflammatory pathways and contact-mediated coagulation. We investigated if modulation of the thromboinflammatory response improves outcomes in hospitalized COVID-19 patients. METHODS In this multicenter open-label randomized clinical trial (EudraCT 2020-001739-28), patients hospitalized with COVID-19 were 1:2 randomized to receive standard of care (SOC) or SOC plus study intervention. The intervention consisted of aprotinin (2,000,000 IE IV four times daily) combined with low molecular weight heparin (LMWH; SC 50 IU/kg twice daily on the ward, 75 IU/kg twice daily in intensive care). Additionally, patients with predefined hyperinflammation received the interleukin-1 receptor antagonist anakinra (100 mg IV four times daily). The primary outcome was time to a sustained 2-point improvement on the 7-point World Health Organization ordinal scale for clinical status, or discharge. FINDINGS Between 24 June 2020 and 1 February 2021, 105 patients were randomized, and 102 patients were included in the full analysis set (intervention N = 67 vs. SOC N = 35). Twenty-five patients from the intervention group (37%) received anakinra. The intervention did not affect the primary outcome (HR 0.77 [CI 0.50-1.19], p = 0.24) or mortality (intervention n = 3 [4.6%] vs. SOC n = 2 [5.7%], HR 0.82 [CI 0.14-4.94], p = 0.83). There was one treatment-related adverse event in the intervention group (hematuria, 1.49%). There was one thrombotic event in the intervention group (1.49%) and one in the SOC group (2.86%), but no major bleeding. CONCLUSIONS In hospitalized COVID-19 patients, modulation of thromboinflammation with high-dose aprotinin and LMWH with or without anakinra did not improve outcome in patients with moderate to severe COVID-19.
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Comparison of the efficacy and safety of intralesional injection of tranexamic acid and the topical application of Kligman combination drug in the treatment of macular amyloidosis
Ghassemi, M., Roohaninasab, M., Kamani, S. A., Sadeghzadeh-Bazargan, A., Goodarzi, A.
Dermatologic Therapy. 2022;35(1):e15213
Abstract
Macular amyloidosis (MA) is a common form of cutaneous amyloidosis that manifests as dark spots consisting of brown pigments with a rippled pattern on the skin, and the treatment of this condition is highly challenging. The aim of this study was to compare the efficacy and safety of intralesional injection of tranexamic acid (TXA) and topical application of Kligman combination drug in the treatment of macular amyloidosis. In this double-blind clinical trial, a total of 43 patients, who were diagnosed with MA, were treated with two different methods of intralesional injection of tranexamic acid and topical application of Kligman combination drug. Both therapeutic methods were effective in improving MA and significantly reduced hyperpigmentation of the treated areas, but tranexamic acid was significantly more effective than the Kligman combination drug. Significantly, greater improvements were observed in the group of patients treated with tranexamic acid. In the tranexamic acid treatment group, ΔE was reduced from 11.39 in the first session to 8.53 in the third session, and in the Kligman treatment group, it was reduced from 8.79 in the first session to 6.32 in the third session (p < 0.05). In addition, the pruritus score in patients treated with topical tranexamic acid injection was lower compared to the patients treated with the topical application of the Kligman combination drug. The results of this study demonstrated the significant positive effects of both treatment methods, but in terms of reducing melanin content, intralesional injection of tranexamic acid was a more effective method. Both treatments considered safe for MA. In tranexamic acid group, patients logically experienced a tolerable pain during injection but they significantly had significantly lower local pruritic discomfort during study. So, based on the positive findings of this study we suggest to use tranexamic acid in combination with other effective therapeutic methods for treatment of MA especially use of its topically applied form in combination with non-aggressive needling that results in better drug delivery without the experience of injection pain. Selection of the best administration route of tranexamic acid for hyperpigmented lesions depends on the each patient characteristic and their previous theraputic results that may vary case by case.
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Analysis of Relapse by Inflammatory Rasch-built Overall Disability Scale Status in the PATH Study of Subcutaneous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy
Merkies ISJ, van Schaik IN, Bril V, Hartung HP, Lewis RA, Sobue G, Lawo JP, Mielke O, Cornblath DR
Journal of the peripheral nervous system : JPNS. 2022
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BACKGROUND AND AIMS Clinical trials in chronic inflammatory demyelinating polyneuropathy (CIDP) often assess efficacy using the ordinal Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Here, data from the PATH study was reanalyzed using change in Inflammatory Rasch-built Overall Disability Scale (I-RODS) to define CIDP relapse instead of INCAT. METHODS The PATH study comprised an intravenous immunoglobulin (IVIG) dependency period and an IVIG (IgPro10 [Privigen®]) restabilization period; subjects were then randomized to weekly maintenance subcutaneous immunoglobulin (SCIG; IgPro20 [Hizentra®]) 0.2 g/kg or 0.4 g/kg or placebo for 24 weeks. CIDP relapse was defined as ≥1-point deterioration in adjusted INCAT, with a primary endpoint of relapse or withdrawal rates. This retrospective exploratory analysis redefined relapse using I-RODS via three different cut-off methods: an individual variability method, fixed cut-off of ≥8-point deterioration on I-RODS centile score or ≥4-point deterioration on I-RODS raw score. RESULTS Relapse or withdrawal rates were 47% for placebo, 34% for 0.2 g/kg IgPro20 and 19% for 0.4 g/kg IgPro20 using the raw score; 40%, 28% and 15%, respectively using the centile score, and 49%, 40% and 27%, respectively using the individual variability method. INTERPRETATION IgPro20 was shown to be efficacious as a maintenance therapy for CIDP when relapse was defined using I-RODS. A stable response pattern was shown for I-RODS across various applied cut-offs, indicating that any could be used in future clinical trials.
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Effect of Tranexamic Acid Administration on Remote Cerebral Ischemic Lesions in Acute Spontaneous Intracerebral Hemorrhage: A Substudy of a Randomized Clinical Trial
Pszczolkowski S, Sprigg N, Woodhouse LJ, Gallagher R, Swienton D, Law ZK, Casado AM, Roberts I, Werring DJ, Al-Shahi Salman R, et al
JAMA neurology. 2022
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IMPORTANCE Hyperintense foci on diffusion-weighted imaging (DWI) that are spatially remote from the acute hematoma occur in 20% of people with acute spontaneous intracerebral hemorrhage (ICH). Tranexamic acid, a hemostatic agent that is under investigation for treating acute ICH, might increase DWI hyperintense lesions (DWIHLs). OBJECTIVE To establish whether tranexamic acid compared with placebo increased the prevalence or number of remote cerebral DWIHLs within 2 weeks of ICH onset. DESIGN, SETTING, AND PARTICIPANTS This prospective nested magnetic resonance imaging (MRI) substudy of a randomized clinical trial (RCT) recruited participants from the multicenter, double-blind, placebo-controlled, phase 3 RCT (Tranexamic Acid for Hyperacute Primary Intracerebral Hemorrhage [TICH-2]) from July 1, 2015, to September 30, 2017, and conducted follow-up to 90 days after participants were randomized to either the tranexamic acid or placebo group. Participants had acute spontaneous ICH and included TICH-2 participants who provided consent to undergo additional MRI scans for the MRI substudy and those who had clinical MRI data that were compatible with the brain MRI protocol of the substudy. Data analyses were performed on an intention-to-treat basis on January 20, 2020. INTERVENTIONS The tranexamic acid group received 1 g in 100-mL intravenous bolus loading dose, followed by 1 g in 250-mL infusion within 8 hours of ICH onset. The placebo group received 0.9% saline within 8 hours of ICH onset. Brain MRI scans, including DWI, were performed within 2 weeks. MAIN OUTCOMES AND MEASURES Prevalence and number of remote DWIHLs were compared between the treatment groups using binary logistic regression adjusted for baseline covariates. RESULTS A total of 219 participants (mean [SD] age, 65.1 [13.8] years; 126 men [57.5%]) who had brain MRI data were included. Of these participants, 96 (43.8%) were randomized to receive tranexamic acid and 123 (56.2%) were randomized to receive placebo. No baseline differences in demographic characteristics and clinical or imaging features were found between the groups. There was no increase for the tranexamic acid group compared with the placebo group in DWIHL prevalence (20 of 96 [20.8%] vs 28 of 123 [22.8%]; odds ratio [OR], 0.71; 95% CI, 0.33-1.53; P = .39) or mean (SD) number of DWIHLs (1.75 [1.45] vs 1.81 [1.71]; mean difference [MD], -0.08; 95% CI, -0.36 to 0.20; P = .59). In an exploratory analysis, participants who were randomized within 3 hours of ICH onset or those with chronic infarcts appeared less likely to have DWIHLs if they received tranexamic acid. Participants with probable cerebral amyloid angiopathy appeared more likely to have DWIHLs if they received tranexamic acid. CONCLUSIONS AND RELEVANCE This substudy of an RCT found no evidence of increased prevalence or number of remote DWIHLs after tranexamic acid treatment in acute ICH. These findings provide reassurance for ongoing and future trials that tranexamic acid for acute ICH is unlikely to induce cerebral ischemic events. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN93732214.
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A high-dose 24-hour tranexamic acid infusion for the treatment of significant gastrointestinal bleeding: HALT-IT RCT
Roberts, I., Shakur-Still, H., Afolabi, A., Akere, A., Arribas, M., Austin, E., Bal, K., Bazeer, N., Beaumont, D., Brenner, A., et al
Health Technology Assessment (Winchester, England). 2021;25(58):1-86
Abstract
BACKGROUND Tranexamic acid reduces blood loss in surgery and the risk of death in trauma patients. Meta-analyses of small trials suggest that tranexamic acid decreases the number of deaths from gastrointestinal bleeding, but these meta-analyses are prone to selection bias. OBJECTIVE The trial provides reliable evidence of the effect of tranexamic acid on mortality, rebleeding and complications in significant acute gastrointestinal bleeding. DESIGN A multicentre, randomised, placebo-controlled trial and economic analysis. Patients were assigned by selecting one treatment pack from a box of eight, which were identical apart from the pack number. Patients, caregivers and outcome assessors were masked to allocation. The main analyses were by intention to treat. SETTING The setting was 164 hospitals in 15 countries, co-ordinated from the London School of Hygiene & Tropical Medicine. PARTICIPANTS Adults with significant upper or lower gastrointestinal bleeding (n = 12,009) were eligible if the responsible clinician was substantially uncertain about whether or not to use tranexamic acid. The clinical diagnosis of significant bleeding implied a risk of bleeding to death, including hypotension, tachycardia or signs of shock, or urgent transfusion, endoscopy or surgery. INTERVENTION Tranexamic acid (a 1-g loading dose over 10 minutes, then a 3-g maintenance dose over 24 hours) or matching placebo. MAIN OUTCOME MEASURES The primary outcome was death due to bleeding within 5 days of randomisation. Secondary outcomes were all-cause and cause-specific mortality; rebleeding; need for endoscopy, surgery or radiological intervention; blood product transfusion; complications; disability; and days spent in intensive care or a high-dependency unit. RESULTS A total of 12,009 patients were allocated to receive tranexamic acid (n = 5994, 49.9%) or the matching placebo (n = 6015, 50.1%), of whom 11,952 (99.5%) received the first dose. Death due to bleeding within 5 days of randomisation occurred in 222 (3.7%) patients in the tranexamic acid group and in 226 (3.8%) patients in the placebo group (risk ratio 0.99, 95% confidence interval 0.82 to 1.18). Thromboembolic events occurred in 86 (1.4%) patients in the tranexamic acid group and 72 (1.2%) patients in the placebo group (risk ratio 1.20, 95% confidence interval 0.88 to 1.64). The risk of arterial thromboembolic events (myocardial infarction or stroke) was similar in both groups (0.7% in the tranexamic acid group vs. 0.8% in the placebo group; risk ratio 0.92, 95% confidence interval 0.60 to 1.39), but the risk of venous thromboembolic events (deep-vein thrombosis or pulmonary embolism) was higher in tranexamic acid-treated patients than in placebo-treated patients (0.8% vs. 0.4%; risk ratio 1.85, 95% confidence interval 1.15 to 2.98). Seizures occurred in 38 patients who received tranexamic acid and in 22 patients who received placebo (0.6% vs. 0.4%, respectively; risk ratio 1.73, 95% confidence interval 1.03 to 2.93). In the base-case economic analysis, tranexamic acid was not cost-effective and resulted in slightly poorer health outcomes than no tranexamic acid. CONCLUSIONS Tranexamic acid did not reduce death from gastrointestinal bleeding and, although inexpensive, it is not cost-effective in adults with acute gastrointestinal bleeding. FUTURE WORK These results caution against a uniform approach to the management of patients with major haemorrhage and highlight the need for randomised trials targeted at specific pathophysiological processes. LIMITATIONS Although this is one of the largest randomised trials in gastrointestinal bleeding, we cannot rule out a modest increase or decrease in death due to bleeding with tranexamic acid. TRIAL REGISTRATION Current Controlled Trials ISRCTN11225767, ClinicalTrials.gov NCT01658124 and EudraCT 2012-003192-19. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 58. See the NIHR Journals Library website for further project information.