Ignite Creation Date:
2024-05-06 @ 7:51 AM
Last Modification Date:
2024-10-26 @ 11:53 AM
Study NCT ID:
NCT02618980
Status:
TERMINATED
Last Update Posted:
2021-12-20
First Post:
2015-11-21
Brief Title:
Early Endoscopy for Acute Upper Gastrointestinal Bleeding in Acute Coronary Syndrome Patients
Sponsor:
Far Eastern Memorial Hospital
Organization:
Far Eastern Memorial Hospital
Study Overview
Official Title:
Management of Acute Upper Gastrointestinal Bleeding in Recent Acute Coronary Syndrome Patients by Early Endoscopy and Non-Endoscopy Treatment A Randomized Controlled Trial to Evaluate Efficacy and Safety
Status:
TERMINATED
Status Verified Date:
2021-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Slow enrollment speed due to the incidence of UGI bleeding in ACS patient is lower than expected
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The primary aim of this study is to compare efficacy of early endoscopy and non-endoscopic treatment for management of acute upper gastrointestinal UGI bleeding in patients with recent acute coronary syndrome ACS This study will also compare rates of surgery repeated intervention endoscopy or TAE rebleeding and complications between two groups
Detailed Description:
MATERIALS AND METHODS Study Design and Randomization A multicenter RCT of recent ACS patients presenting with acute UGIB was conducted in three tertiary centers Far Eastern Memorial Hospital Hsin-Chu Branch and Taipei Branch of National Taiwan University Hospital in Taiwan Patients with recent ACS including unstable angina UA ST-elevation MI STEMI and non-ST elevation MI NSTEMI who presented symptoms of acute UGIB were evaluated for enrollment The inclusion criteria were as follows 1 age over 20-year-old 2 ACS episodes in the past 2 weeks 3 symptoms of UGIB including hematemesis coffee ground emesis or tarry stool passage accompanied with a decrease in hemoglobin Hb level greater than 2 gdl from baseline Patients with any one of the following criteria were excluded 1 malignancy or other advanced disease with a life expectancy of 6 months 2 pregnant or lactating women 3 history of allergy or severe side effects from PPIs contrast and iodine 4 platelet count 80kuL or prothrombin time INR 20 5 decompensated Child-Turcotte-Pugh score B and C liver cirrhosis 6 stage 35 chronic kidney disease CKD estimated Ccr 60 mlmin173m2 using Cockcroft-Gault formula exclusive of end-stage renal disease under renal replacement therapy17 All the authors had access to the study data and had reviewed and approved the final manuscript
Eligible patients were randomly assigned to EE or non-EE management Patients in both groups received bolus intravenous pantoprazole 40mg followed by continuous infusion 8mghour318 In the EE group patients underwent endoscopy within 24 hours after onset of UGIB symptoms All enrolled patients were monitored in cardiac intensive care unit At endoscopy stigmata of hemorrhage SRH were treated by endoscopic therapy in combination of any two of the followings epinephrine submucosal injection thermocoagulation hemoclipping and argon plasma coagulation Hemostasis was considered initial successful if bleeding had stopped at endoscopy Antral-biopsy specimens were obtained to a rapid urease test and histopathological examination for Helicobacter pylori Hp study Patients assigned to non-EE group received medical treatment with PPIs alone and underwent esophagogastroduodenoscopy two weeks after enrollment to evaluate the recent SRH Decision on discontinuation of DAPT was at the discretion of cardiologists depending on cardiac conditions of each enrolled patient
Study Endpoints The primary endpoint was failure of control hemorrhage The secondary endpoints included complication rate length of hospital stay units of blood transfusion re-bleeding rate needs for repeated intervention endoscopic therapy transarterial embolization TAE or surgery for uncontrollable recurrent bleeding Blood troponin-T creatine kinase-MB Hb hematocrit Hct and complete electrocardiogram ECG were checked every 8 hours within 24 hours after enrollment APACHE II Rockall and Blatchford scores at intervention were calculated19 This study was approved by the Research Ethics Review Committee of study institutes FEMH IRB-103062-F Hsin-Chu NTUH 105-001-F Yun-Lin NTUH 201411020RIND
Definition of failure to control hemorrhage The time frame for acute bleeding episode was defined as 24 hours after enrollment Clinical failure of control bleeding was defined as hematemesis or nasogastric tube drainage of significant fresh blood 200 mL 2hours or persistent hypovolemic shock after intervention or 3 gdl drop in Hb level or 9 drop of Hct within 24 hours if no blood transfusion or a decrease in Hb 2 gdL or an increase 1 gdL despite 2 or more units of red blood cells RBC component transfusion within 24 hours
Definition of re-bleeding
Clinically significant recurrent bleeding was defined by the followings vomiting of fresh blood fresh blood in the nasogastric tube aspirate hematochezia or melena after a normal color stool and a decrease in Hb 2 gdL or an increase less than 1 gdL despite 2 or more units of RBC component transfusion
Definition of major and minor complications Major complications were defined as death and life-threatening arrhythmias within 24 hours after randomization Minor complications were defined as hypotension 9060mmHg hypertension 180100mmHg tachycardia 120bpm bradycardia 60bpm tachypnea 24min oxygen desaturation SpO2 90 and minor arrhythmias
Sample Size Estimation and Randomization The null hypothesis of this study was the superiority of EE over non-EE in the efficacy on bleeding control The primary efficacy analysis used an intention-to-treat approach that included all patients meeting the entry criteria who had completed the follow-up Approximately 80 of UGIB patients will stop bleeding spontaneously20 and rates of hemostasis that resulted from a first endoscopic procedure exceeded 94 in most large studies21 However there was no data demonstrating the outcome of patients under DAPT developing acute UGIB treated medically alone Therefore we assumed that about 70 of acute UGIB patients under DAPT would stop bleeding spontaneously without therapeutic endoscopy As a result we estimated a sample size of at least totally 78 patients in EE and non-EE groups in order to achieve a statistical power of 80 at a 5 significance level on a two-tailed test with margin of error of 2 in order to detect a 24 94 vs 70 difference Sealed envelopes with computer generated randomization number 0 for non-EE 1 for EE group were used After enrollment gastroenterologists opened the consecutive envelops for randomization
Statistical Analysis Continuous variables were expressed as mean standard deviation and the comparisons between two groups were performed using the Student t-test categorical variables were summarized as count and the comparisons between groups were made using the Chi-square or the Fishers exact test when appropriate Univariate and multivariate logistic regression models were performed for evaluation of the risk factors for outcomes in both groups A two-tailed p value 005 was considered as statistically significant The statistical analysis was performed using STATA software version 110 Stata Corp College Station TX USA
Eligible patients were randomly assigned to EE or non-EE management Patients in both groups received bolus intravenous pantoprazole 40mg followed by continuous infusion 8mghour318 In the EE group patients underwent endoscopy within 24 hours after onset of UGIB symptoms All enrolled patients were monitored in cardiac intensive care unit At endoscopy stigmata of hemorrhage SRH were treated by endoscopic therapy in combination of any two of the followings epinephrine submucosal injection thermocoagulation hemoclipping and argon plasma coagulation Hemostasis was considered initial successful if bleeding had stopped at endoscopy Antral-biopsy specimens were obtained to a rapid urease test and histopathological examination for Helicobacter pylori Hp study Patients assigned to non-EE group received medical treatment with PPIs alone and underwent esophagogastroduodenoscopy two weeks after enrollment to evaluate the recent SRH Decision on discontinuation of DAPT was at the discretion of cardiologists depending on cardiac conditions of each enrolled patient
Study Endpoints The primary endpoint was failure of control hemorrhage The secondary endpoints included complication rate length of hospital stay units of blood transfusion re-bleeding rate needs for repeated intervention endoscopic therapy transarterial embolization TAE or surgery for uncontrollable recurrent bleeding Blood troponin-T creatine kinase-MB Hb hematocrit Hct and complete electrocardiogram ECG were checked every 8 hours within 24 hours after enrollment APACHE II Rockall and Blatchford scores at intervention were calculated19 This study was approved by the Research Ethics Review Committee of study institutes FEMH IRB-103062-F Hsin-Chu NTUH 105-001-F Yun-Lin NTUH 201411020RIND
Definition of failure to control hemorrhage The time frame for acute bleeding episode was defined as 24 hours after enrollment Clinical failure of control bleeding was defined as hematemesis or nasogastric tube drainage of significant fresh blood 200 mL 2hours or persistent hypovolemic shock after intervention or 3 gdl drop in Hb level or 9 drop of Hct within 24 hours if no blood transfusion or a decrease in Hb 2 gdL or an increase 1 gdL despite 2 or more units of red blood cells RBC component transfusion within 24 hours
Definition of re-bleeding
Clinically significant recurrent bleeding was defined by the followings vomiting of fresh blood fresh blood in the nasogastric tube aspirate hematochezia or melena after a normal color stool and a decrease in Hb 2 gdL or an increase less than 1 gdL despite 2 or more units of RBC component transfusion
Definition of major and minor complications Major complications were defined as death and life-threatening arrhythmias within 24 hours after randomization Minor complications were defined as hypotension 9060mmHg hypertension 180100mmHg tachycardia 120bpm bradycardia 60bpm tachypnea 24min oxygen desaturation SpO2 90 and minor arrhythmias
Sample Size Estimation and Randomization The null hypothesis of this study was the superiority of EE over non-EE in the efficacy on bleeding control The primary efficacy analysis used an intention-to-treat approach that included all patients meeting the entry criteria who had completed the follow-up Approximately 80 of UGIB patients will stop bleeding spontaneously20 and rates of hemostasis that resulted from a first endoscopic procedure exceeded 94 in most large studies21 However there was no data demonstrating the outcome of patients under DAPT developing acute UGIB treated medically alone Therefore we assumed that about 70 of acute UGIB patients under DAPT would stop bleeding spontaneously without therapeutic endoscopy As a result we estimated a sample size of at least totally 78 patients in EE and non-EE groups in order to achieve a statistical power of 80 at a 5 significance level on a two-tailed test with margin of error of 2 in order to detect a 24 94 vs 70 difference Sealed envelopes with computer generated randomization number 0 for non-EE 1 for EE group were used After enrollment gastroenterologists opened the consecutive envelops for randomization
Statistical Analysis Continuous variables were expressed as mean standard deviation and the comparisons between two groups were performed using the Student t-test categorical variables were summarized as count and the comparisons between groups were made using the Chi-square or the Fishers exact test when appropriate Univariate and multivariate logistic regression models were performed for evaluation of the risk factors for outcomes in both groups A two-tailed p value 005 was considered as statistically significant The statistical analysis was performed using STATA software version 110 Stata Corp College Station TX USA
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None