scholarly journals Tranexamic acid for acute intracerebral haemorrhage growth based on imaging assessment (TRAIGE): a multicentre, randomised, placebo-controlled trial

2021 ◽  
pp. svn-2021-000942
Author(s):  
Jingyi Liu ◽  
Ximing Nie ◽  
Hongqiu Gu ◽  
Qi Zhou ◽  
Haixin Sun ◽  
...  
Keyword(s):  
Placebo Group ◽  
Tranexamic Acid ◽  
Intracerebral Haemorrhage ◽  
Intracranial Haemorrhage ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Intracerebral Haematoma ◽  
Spot Sign ◽  
Double Blind ◽  
Risk Of Death

BackgroundStudies show tranexamic acid can reduce the risk of death and early neurological deterioration after intracranial haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in intracerebral haemorrhage patients susceptible to haemorrhage expansion.MethodsWe did a prospective, double-blind, randomised, placebo-controlled trial at 10 stroke centres in China. Acute supratentorial intracerebral haemorrhage patients were eligible if they had indication of haemorrhage expansion on admission imaging (eg, spot sign, black hole sign or blend sign), and were treatable within 8 hours of symptom onset. Patients were randomly assigned (1:1) to receive either tranexamic acid or a matching placebo. The primary outcome was intracerebral haematoma growth (>33% relative or >6 mL absolute) at 24 hours. Clinical outcomes were assessed at 90 days.ResultsOf the 171 included patients, 124 (72.5%) were male, and the mean age was 55.9±11.6 years. 89 patients received tranexamic acid and 82 received placebo. The primary outcome did not differ significantly between the groups: 36 (40.4%) patients in the tranexamic acid group and 34 (41.5%) patients in the placebo group had intracranial haemorrhage growth (OR 0.96, 95% CI 0.52 to 1.77, p=0.89). The proportion of death was lower in the tranexamic acid treatment group than placebo group (8.1% vs 10.0%), but there were no significant differences in secondary outcomes including absolute intracranial haemorrhage growth, death and dependency.ConclusionsAmong patients susceptible to haemorrhage expansion treated within 8 hours of stroke onset, tranexamic acid did not significantly prevent intracerebral haemorrhage growth. Larger studies are needed to assess safety and efficacy of tranexamic acid in intracerebral haemorrhage patients.

scholarly journals Tranexamic acid for acute gastrointestinal bleeding (The HALT-IT trial): Statistical analysis plan for an international, randomised, double blind, placebo-controlled trial

2019 ◽  
Author(s):  
Amy Charlotte Brenner ◽  
Adefemi Afolabi ◽  
Syed Masroor Ahmad ◽  
Monica Arribas ◽  
Rizwana Chaudhri ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Blood Transfusion ◽  
Tranexamic Acid ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Gi Bleeding ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Upper Gi ◽  
Lower Gi Bleeding

Abstract Background: Acute gastrointestinal (GI) bleeding is an important cause of mortality worldwide. Bleeding can occur from the upper or lower GI tract, with upper GI bleeding accounting for most cases. The main causes include peptic ulcer / erosive mucosal disease, oesophageal varices and malignancy. The case fatality rate is around 10% for upper GI bleeding and 3% for lower GI bleeding. Rebleeding affects 5-40% of patients and is associated with a four-fold increased risk of death. Tranexamic acid (TXA) decreases bleeding and the need for blood transfusion in surgery and reduces death due to bleeding in patients with trauma and postpartum haemorrhage. It reduces bleeding by inhibiting the breakdown of fibrin clots by plasmin. Due to the methodological weaknesses and small size of the existing trials, the effectiveness and safety of TXA in GI bleeding is uncertain. The HALT-IT trial aims to provide reliable evidence about the effects of TXA in acute upper and lower GI bleeding. Methods: The HALT-IT trial is an international, randomised, double blind, placebo-controlled trial of tranexamic acid in 12,000 adults (increased from 8,000) with acute upper or lower GI bleeding. Eligible patients are randomly allocated to receive tranexamic acid (1g loading dose followed by 3g maintenance dose over 24 hours) or matching placebo. The main analysis will compare those randomised to tranexamic acid with those randomised to placebo on an intention-to-treat basis, presenting the results as effect estimates (relative and absolute risks) and confidence intervals. The primary outcome is death due to bleeding within 5 days of randomisation and secondary outcomes are rebleeding, all-cause and cause-specific mortality, thromboembolic events, complications, endoscopic, radiological and surgical interventions, blood transfusion requirements, disability (defined by a measure of patient’s self-care capacity) and number of days spent in intensive care or high dependency units. Subgroup analyses for the primary outcome will consider time to treatment, location of bleeding, cause of bleed and clinical Rockall score. Discussion: We present the statistical analysis of the HALT-IT trial. This plan was prepared and submitted for publication before the treatment allocation was un-blinded. Trial Registration: Current Controlled Trials ISRCTN11225767 (3/07/2012); Clinicaltrials.gov NCT01658124 (26/07/2012). Keywords: Gastrointestinal haemorrhage, tranexamic acid, clinical trial, statistical analysis.

scholarly journals Effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery: multicentre, double blind, randomised controlled trial

BMJ ◽  
2021 ◽  
pp. n1162
Author(s):  
Karim Asehnoune ◽  
Charlene Le Moal ◽  
Gilles Lebuffe ◽  
Marguerite Le Penndu ◽  
Nolwen Chatel Josse ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Placebo Group ◽  
Odds Ratio ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Double Blind ◽  
Intention To Treat ◽  
Dexamethasone Group ◽  
All Cause Mortality ◽  
Treat Population

Abstract Objective To assess the effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery. Design Phase III, randomised, double blind, placebo controlled trial. Setting 34 centres in France, December 2017 to March 2019. Participants 1222 adults (>50 years) requiring major non-cardiac surgery with an expected duration of more than 90 minutes. The anticipated time frame for recruitment was 24 months. Interventions Participants were randomised to receive either dexamethasone (0.2 mg/kg immediately after the surgical procedure, and on day 1) or placebo. Randomisation was stratified on the two prespecified criteria of cancer and thoracic procedure. Main outcomes measures The primary outcome was a composite of postoperative complications or all cause mortality within 14 days after surgery, assessed in the modified intention-to-treat population (at least one treatment administered). Results Of the 1222 participants who underwent randomisation, 1184 (96.9%) were included in the modified intention-to-treat population. 14 days after surgery, 101 of 595 participants (17.0%) in the dexamethasone group and 117 of 589 (19.9%) in the placebo group had complications or died (adjusted odds ratio 0.81, 95% confidence interval 0.60 to 1.08; P=0.15). In the stratum of participants who underwent non-thoracic surgery (n=1038), the primary outcome occurred in 69 of 520 participants (13.3%) in the dexamethasone group and 93 of 518 (18%) in the placebo group (adjusted odds ratio 0.70, 0.50 to 0.99). Adverse events were reported in 288 of 613 participants (47.0%) in the dexamethasone group and 296 of 609 (48.6%) in the placebo group (P=0.46). Conclusions Dexamethasone was not found to significantly reduce the incidence of complications and death in patients 14 days after major non-cardiac surgery. The 95% confidence interval for the main result was, however, wide and suggests the possibility of important clinical effectiveness. Trial registration ClinicalTrials.gov NCT03218553 .

scholarly journals Outcomes in Antiplatelet‐Associated Intracerebral Hemorrhage in the TICH‐2 Randomized Controlled Trial

2021 ◽  
Author(s):  
Zhe Kang Law ◽  
Michael Desborough ◽  
Ian Roberts ◽  
Rustam Al‐Shahi Salman ◽  
Timothy J. England ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Tranexamic Acid ◽  
Functional Outcome ◽  
Antiplatelet Therapy ◽  
Controlled Trial ◽  
Hematoma Expansion ◽  
Modified Rankin Scale ◽  
Double Blind ◽  
Risk Of Death ◽  
Increased Risk

Background Antiplatelet therapy increases the risk of hematoma expansion in intracerebral hemorrhage (ICH) while the effect on functional outcome is uncertain. Methods and Results This is an exploratory analysis of the TICH‐2 (Tranexamic Acid in Intracerebral Hemorrhage‐2) double‐blind, randomized, placebo‐controlled trial, which studied the efficacy of tranexamic acid in patients with spontaneous ICH within 8 hours of onset. Multivariable logistic regression and ordinal regression were performed to explore the relationship between pre‐ICH antiplatelet therapy, and 24‐hour hematoma expansion and day 90 modified Rankin Scale score, as well as the effect of tranexamic acid. Of 2325 patients, 611 (26.3%) had pre‐ICH antiplatelet therapy. They were older (mean age, 75.7 versus 66.5 years), more likely to have ischemic heart disease (25.4% versus 2.7%), ischemic stroke (36.2% versus 6.3%), intraventricular hemorrhage (40.2% versus 27.5%), and larger baseline hematoma volume (mean, 28.1 versus 22.6 mL) than the no‐antiplatelet group. Pre‐ICH antiplatelet therapy was associated with a significantly increased risk of hematoma expansion (adjusted odds ratio [OR], 1.28; 95% CI, 1.01–1.63), a shift toward unfavorable outcome in modified Rankin Scale (adjusted common OR, 1.58; 95% CI, 1.32–1.91) and a higher risk of death at day 90 (adjusted OR, 1.63; 95% CI, 1.25–2.11). Tranexamic acid reduced the risk of hematoma expansion in the overall patients with ICH (adjusted OR, 0.76; 95% CI, 0.62–0.93) and antiplatelet subgroup (adjusted OR, 0.61; 95% CI, 0.41–0.91) with no significant interaction between pre‐ICH antiplatelet therapy and tranexamic acid (P interaction=0.248). Conclusions Antiplatelet therapy is independently associated with hematoma expansion and unfavorable functional outcome. Tranexamic acid reduced hematoma expansion regardless of prior antiplatelet therapy use. Registration URL: https://www.isrctn.com ; Unique identifier: ISRCTN93732214.

scholarly journals Tranexamic acid for acute gastrointestinal bleeding (The HALT-IT trial): Statistical analysis plan for an international, randomised, double blind, placebo-controlled trial

2019 ◽  
Author(s):  
Amy Charlotte Brenner ◽  
Adefemi Afolabi ◽  
Syed Masroor Ahmad ◽  
Monica Arribas ◽  
Rizwana Chaudhri ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Blood Transfusion ◽  
Tranexamic Acid ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Gi Bleeding ◽  
Double Blind ◽  
Upper Gi Bleeding ◽  
Upper Gi ◽  
Lower Gi Bleeding

Abstract Background: Acute gastrointestinal (GI) bleeding is an important cause of mortality worldwide. Bleeding can occur from the upper or lower GI tract, with upper GI bleeding accounting for most cases. The main causes include peptic ulcer / erosive mucosal disease, oesophageal varices and malignancy. The case fatality rate is around 10% for upper GI bleeding and 3% for lower GI bleeding. Rebleeding affects 5-40% of patients and is associated with a four-fold increased risk of death. Tranexamic acid (TXA) decreases bleeding and the need for blood transfusion in surgery and reduces death due to bleeding in patients with trauma and postpartum haemorrhage. It reduces bleeding by inhibiting the breakdown of fibrin clots by plasmin. Due to the methodological weaknesses and small size of the existing trials, the effectiveness and safety of TXA in GI bleeding is uncertain. The HALT-IT trial aims to provide reliable evidence about the effects of TXA in acute upper and lower GI bleeding. Methods: The HALT-IT trial is an international, randomised, double blind (participant and trial staff), placebo-controlled trial of tranexamic acid in 12,000 adults (increased from 8,000) with acute upper or lower GI bleeding. Eligible patients are randomly allocated to receive tranexamic acid (1g loading dose followed by 3g maintenance dose over 24 hours) or matching placebo. The main analysis will compare those randomised to tranexamic acid with those randomised to placebo on an intention-to-treat basis, presenting the results as effect estimates (relative risks) and confidence intervals. The primary outcome is death due to bleeding within 5 days of randomisation and secondary outcomes are rebleeding, all-cause and cause-specific mortality, thromboembolic events, complications, endoscopic, radiological and surgical interventions, blood transfusion requirements, disability (defined by a measure of patient’s self-care capacity) and number of days spent in intensive care or high dependency units. Subgroup analyses for the primary outcome will consider time to treatment, location of bleeding, cause of bleed and clinical Rockall score. Discussion: We present the statistical analysis of the HALT-IT trial. This plan was published before the treatment allocation was un-blinded.

scholarly journals Tranexamic acid for acute gastrointestinal bleeding (The HALT-IT trial): Statistical analysis plan for an international, randomised, double blind, placebo-controlled trial

2019 ◽  
Author(s):  
Amy Charlotte Brenner ◽  
Adefemi Afolabi ◽  
Syed Masroor Ahmad ◽  
Monica Arribas ◽  
Rizwana Chaudhri ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Blood Transfusion ◽  
Tranexamic Acid ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Gi Bleeding ◽  
Double Blind ◽  
Upper Gi Bleeding ◽  
Upper Gi ◽  
Lower Gi Bleeding

Abstract Background: Acute gastrointestinal (GI) bleeding is an important cause of mortality worldwide. Bleeding can occur from the upper or lower GI tract, with upper GI bleeding accounting for most cases. The main causes include peptic ulcer / erosive mucosal disease, oesophageal varices and malignancy. The case fatality rate is around 10% for upper GI bleeding and 3% for lower GI bleeding. Rebleeding affects 5-40% of patients and is associated with a four-fold increased risk of death. Tranexamic acid (TXA) decreases bleeding and the need for blood transfusion in surgery and reduces death due to bleeding in patients with trauma and postpartum haemorrhage. It reduces bleeding by inhibiting the breakdown of fibrin clots by plasmin. Due to the methodological weaknesses and small size of the existing trials, the effectiveness and safety of TXA in GI bleeding is uncertain. The HALT-IT trial aims to provide reliable evidence about the effects of TXA in acute upper and lower GI bleeding. Methods: The HALT-IT trial is an international, randomised, double blind (participant and trial staff), placebo-controlled trial of tranexamic acid in 12,000 adults (increased from 8,000) with acute upper or lower GI bleeding. Eligible patients are randomly allocated to receive tranexamic acid (1g loading dose followed by 3g maintenance dose over 24 hours) or matching placebo. The main analysis will compare those randomised to tranexamic acid with those randomised to placebo on an intention-to-treat basis, presenting the results as effect estimates (relative and absolute risks) and confidence intervals. The primary outcome is death due to bleeding within 5 days of randomisation and secondary outcomes are rebleeding, all-cause and cause-specific mortality, thromboembolic events, complications, endoscopic, radiological and surgical interventions, blood transfusion requirements, disability (defined by a measure of patient’s self-care capacity) and number of days spent in intensive care or high dependency units. Subgroup analyses for the primary outcome will consider time to treatment, location of bleeding, cause of bleed and clinical Rockall score. Discussion: We present the statistical analysis of the HALT-IT trial. This plan was published before the treatment allocation was un-blinded.

scholarly journals Tranexamic acid for acute gastrointestinal bleeding (The HALT-IT trial): Statistical analysis plan for an international, randomised, double blind, placebo-controlled trial

2019 ◽  
Author(s):  
Amy Charlotte Brenner ◽  
Adefemi Afolabi ◽  
Syed Masroor Ahmad ◽  
Monica Arribas ◽  
Rizwana Chaudhri ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Blood Transfusion ◽  
Tranexamic Acid ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Gi Bleeding ◽  
Double Blind ◽  
Upper Gi Bleeding ◽  
Upper Gi ◽  
Lower Gi Bleeding

Abstract Background: Acute gastrointestinal (GI) bleeding is an important cause of mortality worldwide. Bleeding can occur from the upper or lower GI tract, with upper GI bleeding accounting for most cases. The main causes include peptic ulcer / erosive mucosal disease, oesophageal varices and malignancy. The case fatality rate is around 10% for upper GI bleeding and 3% for lower GI bleeding. Rebleeding affects 5-40% of patients and is associated with a four-fold increased risk of death. Tranexamic acid (TXA) decreases bleeding and the need for blood transfusion in surgery and reduces death due to bleeding in patients with trauma and postpartum haemorrhage. It reduces bleeding by inhibiting the breakdown of fibrin clots by plasmin. Due to the methodological weaknesses and small size of the existing trials, the effectiveness and safety of TXA in GI bleeding is uncertain. The HALT-IT trial aims to provide reliable evidence about the effects of TXA in acute upper and lower GI bleeding. Methods: The HALT-IT trial is an international, randomised, double blind (participant and trial staff), placebo-controlled trial of tranexamic acid in 12,000 adults (increased from 8,000) with acute upper or lower GI bleeding. Eligible patients are randomly allocated to receive tranexamic acid (1g loading dose followed by 3g maintenance dose over 24 hours) or matching placebo. The main analysis will compare those randomised to tranexamic acid with those randomised to placebo on an intention-to-treat basis, presenting the results as effect estimates (relative and absolute risks) and confidence intervals. The primary outcome is death due to bleeding within 5 days of randomisation and secondary outcomes are rebleeding, all-cause and cause-specific mortality, thromboembolic events, complications, endoscopic, radiological and surgical interventions, blood transfusion requirements, disability (defined by a measure of patient’s self-care capacity) and number of days spent in intensive care or high dependency units. Subgroup analyses for the primary outcome will consider time to treatment, location of bleeding, cause of bleed and clinical Rockall score. Discussion: We present the statistical analysis of the HALT-IT trial. This plan was published before the treatment allocation was un-blinded.

Double-blind, randomized controlled trial of tranexamic acid in minor lumbar spine surgery: no effect on operative time, intraoperative blood loss, or complications

2019 ◽  
Vol 31 (2) ◽  
pp. 194-200 ◽  
Author(s):  
Signe Elmose ◽  
Mikkel Ø. Andersen ◽  
Else Bay Andresen ◽  
Leah Yacat Carreon
Keyword(s):  
Placebo Group ◽  
Lumbar Spine ◽  
Blood Loss ◽  
Tranexamic Acid ◽  
Spine Surgery ◽  
Operative Time ◽  
Decompressive Surgery ◽  
Lumbar Spine Surgery ◽  
Intraoperative Blood Loss ◽  
Double Blind

OBJECTIVEThe purpose of this study was to investigate the effect of tranexamic acid (TXA) compared to placebo in low-risk adult patients undergoing elective minor lumbar spine surgery—specifically with respect to operative time, estimated blood loss, and complications. Studies have shown that TXA reduces blood loss during major spine surgery. There have been no previous studies on the effect of TXA in minor lumbar spine surgery in which these variables have been evaluated.METHODSThe authors enrolled patients with ASA grades 1 to 2 scheduled to undergo lumbar decompressive surgery at Middelfart Hospital into a double-blind, randomized, placebo-controlled, parallel-group study. Patients with thromboembolic disease, coagulopathy, hypersensitivity to TXA, or a history of convulsion were excluded. Patients were randomly assigned, in blocks of 10, to one of 2 groups, TXA or placebo. Anticoagulation therapy was discontinued 2–7 days preoperatively. Prior to the incision, patients received either a bolus of TXA (10 mg/kg) or an equivalent volume of saline solution (placebo). Independent t-tests were used to compare differences between the 2 groups, with statistical significance set at p < 0.05.RESULTSOf the 250 patients enrolled, 17 patients were excluded, leaving 233 cases for analysis (117 in the TXA group and 116 in the placebo group). The demographics of the 2 groups were similar, except for a higher proportion of women in the TXA group (TXA 50% vs placebo 32%, p = 0.017). There was no significant between-groups difference in operative time (49.53 ± 18.26 vs 54.74 ± 24.49 minutes for TXA and placebo, respectively; p = 0.108) or intraoperative blood loss (55.87 ± 48.48 vs 69.14 ± 83.47 ml for TXA and placebo, respectively; p = 0.702). Postoperative blood loss measured from drain output was 62% significantly lower in the TXA group (13.03 ± 21.82 ml) than in the placebo group (34.61 ± 44.38 ml) (p < 0.001). There was no significant difference in number of dural lesions or postoperative spinal epidural hematomas, and there were no thromboembolic events.CONCLUSIONSTranexamic acid did not have a statistically significant effect on operative time, intraoperative blood loss, or complications. This study gives no evidence to support the routine use of TXA during minor lumbar decompressive surgery.Clinical trial registration no.: NCT03714360 (clinicaltrials.gov)

scholarly journals The Effect of Protein Supplementation versus Carbohydrate Supplementation on Muscle Damage Markers and Soreness Following a 15-km Road Race: A Double-Blind Randomized Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 858
Author(s):  
Dominique S. M. ten Haaf ◽  
Martin A. Flipsen ◽  
Astrid M. H. Horstman ◽  
Hans Timmerman ◽  
Monique A. H. Steegers ◽  
...  
Keyword(s):  
Placebo Group ◽  
Protein Intake ◽  
Muscle Soreness ◽  
Controlled Trial ◽  
Protein Supplementation ◽  
Group Differences ◽  
Double Blind ◽  
Carbohydrate Supplementation ◽  
Protein Group ◽  
Road Race

We assessed whether a protein supplementation protocol could attenuate running-induced muscle soreness and other muscle damage markers compared to iso-caloric placebo supplementation. A double-blind randomized controlled trial was performed among 323 recreational runners (age 44 ± 11 years, 56% men) participating in a 15-km road race. Participants received milk protein or carbohydrate supplementation, for three consecutive days post-race. Habitual protein intake was assessed using 24 h recalls. Race characteristics were determined and muscle soreness was assessed with the Brief Pain Inventory at baseline and 1–3 days post-race. In a subgroup (n = 149) muscle soreness was measured with a strain gauge algometer and creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations were measured. At baseline, no group-differences were observed for habitual protein intake (protein group: 79.9 ± 26.5 g/d versus placebo group: 82.0 ± 26.8 g/d, p = 0.49) and muscle soreness (protein: 0.45 ± 1.08 versus placebo: 0.44 ± 1.14, p = 0.96). Subjects completed the race with a running speed of 12 ± 2 km/h. With the Intention-to-Treat analysis no between-group differences were observed in reported muscle soreness. With the per-protocol analysis, however, the protein group reported higher muscle soreness 24 h post-race compared to the placebo group (2.96 ± 2.27 versus 2.46 ± 2.38, p = 0.039) and a lower pressure muscle pain threshold in the protein group compared to the placebo group (71.8 ± 30.0 N versus 83.9 ± 27.9 N, p = 0.019). No differences were found in concentrations of CK and LDH post-race between groups. Post-exercise protein supplementation is not more preferable than carbohydrate supplementation to reduce muscle soreness or other damage markers in recreational athletes with mostly a sufficient baseline protein intake running a 15-km road race.

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