Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT02618980 |
| Other study ID # |
FEMH-IRB-103062-F |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 2014 |
| Est. completion date |
July 2021 |
Study information
| Verified date |
December 2021 |
| Source |
Far Eastern Memorial Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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 g/dl 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 < 80k/uL, or prothrombin time INR >2.0, 5) decompensated (Child-Turcotte-Pugh score B
and C) liver cirrhosis, 6) stage 3~5 chronic kidney disease (CKD) (estimated Ccr < 60
ml/min/1.73m2) using Cockcroft-Gault formula, exclusive of end-stage renal disease under
renal replacement therapy.17 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 (8mg/hour).3,18
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 calculated.19 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 g/dl drop in Hb level (or 9% drop of
Hct) within 24 hours if no blood transfusion; or a decrease in Hb ≥ 2 g/dL or an increase ≤ 1
g/dL, 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 g/dL or an increase less than 1 g/dL, 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 (<90/60mmHg), hypertension (>180/100mmHg), tachycardia (>120bpm),
bradycardia (<60bpm), tachypnea (>24/min.), 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 spontaneously,20 and rates of hemostasis that resulted from a first endoscopic
procedure exceeded 94% in most large studies.21 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 Fisher's 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 <0.05 was considered as statistically significant. The
statistical analysis was performed using STATA software (version 11.0; Stata Corp, College
Station, TX, USA).
