Acute Lower Gastrointestinal Bleeding
Conditions
Keywords
Early colonoscopy, Stigmata of recent hemorrhage, Rebleeding
Brief summary
This multi-center, randomized controlled trial study is planned to include 162 outpatients with onset of acute lower gastrointestinal bleeding to compare the rate of identification of stigmata of recent hemorrhage (SRH), and other clinical outcomes, including the 30-day rebleeding rate, between 'early' colonoscopy and 'elective' colonoscopy.
Detailed description
All patients will receive early colonoscopy or elective colonoscopy, but they do so by different timing. Early colonoscopy will be performed within 24 h of the initial visit. Elective colonoscopy will be performed between 24 and 96 h after the initial visit.
Interventions
PROCEDUREEarly colonoscopy
Performance of prepared colonoscopy within 24 h of arrival
PROCEDUREElective colonoscopy
Performance of prepared colonoscopy between 24 and 96 h after arrival
Sponsors
Tokyo University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parallel, randomized, superiority trial
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males or females aged ≥ 20 years, presenting with moderate-to-severe hematochezia or melena within 24 h of arrival, defined as (i) more than three occurrences of hematochezia within 8 h, (ii) hemorrhagic shock, or (iii) requiring transfusion. 2. Provision of signed and dated informed consent form. 3. Stated willingness to comply with all study procedures and availability for the duration of the study.
Exclusion criteria
An individual who meets any of the following criteria will be excluded from participation in this study: 1. Patients with hematemesis, black vomiting, or melena. 2. Patients with upper gastrointestinal bleeding, diagnosed by nasogastric tube or upper endoscopy. 3. Patients who have impossible consumed the oral bowel preparation solution. 4. Patients who have undergone computed tomography. 5. Patients who have been diagnosed with peptic ulcer diseases within the previous 10 days. 6. Ulcerative colitis or Crohn's disease patients. 7. Patients who have undergone abdominal surgery within the previous 10 days. 8. Patients who have undergone polypectomy, endoscopic mucosal resection, or endoscopic submucosal dissection of the lower gastrointestinal tract within the previous 10 days. 9. Patients with suspected perforation or peritonitis. 10. Patients with suspected intestinal obstruction. 11. Patients with hemorrhagic shock refractory to infusion or blood transfusion. 12. Patients who have undergone total colectomy. 13. Patients with suspected disseminated intravascular coagulation. 14. Patients with end-stage malignant disease. 15. Patients with severe cardiac failure. 16. Patients with active thrombosis. 17. Patients with severe respiratory failure. 18. Pregnant patients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stigmata of Recent Hemorrhage (SRH) Identification Rate | 0-4 day | Stigmata of Recent Hemorrhage (SRH) based on colonoscopic visualization of lesions, such as diverticulosis, tumor, ulcer, hemorrhoid, angioectasia, and polyps exhibiting active bleeding, a visible vessel, or an adherent clot. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Need for Additional Endoscopic Examinations | 0-34 day | Additional endoscopic examinations will be defined as examinations to achieve hemostasis. |
| Need for Interventional Radiology | 0-34 day | It will be defined as radiology intervention to achieve hemostasis. |
| Need for Surgery | 0-34 day | It will be defined as surgery to achieve hemostasis. |
| Thirty-day Rebleeding Rates | 30 day | Rebleeding will be defined as significant fresh blood loss after an initial colonoscopy with any of the following criteria: i) Hemorrhagic shock, including cold sweat, nausea, syncope, or systolic blood pressure ≤ 90 mmHg. ii) Need for transfusion, according to the guidelines of the Ministry of Health, Labour, and Welfare. iii) Further colonoscopy identifies blood pooling, or iv) SRH in the lower gastrointestinal tract. v) Contrast-enhanced CT identifies extravasation in the colorectal region. However, these examinations will not be performed routinely if rebleeding occurs in the study period. |
| Need for Transfusion During Hospitalization | During hospitalization | It will be defined as the numbers of patients who will need transfusion. |
| Success Rate of Endoscopic Treatment; Number of Participants Achieving Hemostasis With Endoscopic Treatment | 0-4 day | Success rate will be defined as the number achieving hemostasis per total number of attempts at endoscopic hemostasis during colonoscopy examination. |
| Number of Participants With Thirty-day Thrombosis Events | 30 day | Thrombosis events will include acute coronary syndromes, including angina pectoris and myocardial infarction, stroke, including cerebrovascular infarction, cerebral hemorrhage, and transient ischemic attacks, deep vein thrombosis, and pulmonary embolism. |
| Number of Participants With Thirty-day Death Events | 30 day | Number of Participants with Thirty-day death Events from enrollment |
| Number of Participants With Preparation-related Adverse Events | 0-4 day | Preparation-related adverse events will include nausea, vomiting, abdominal pain, volume overload, aspiration pneumonia, hemorrhagic shock, exacerbation bleeding, and ileus |
| Number of Participants With Colonoscopy-related Adverse Events | 0-4 day | Colonoscopy-related adverse events will include hemorrhagic shock, and perforation. |
| Length of Stay | 0-34 day | It will be defined as length of stay to cure acute lower gastrointestinal bleeding. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Early Colonoscopy Performance of prepared colonoscopy within 24 h of arrival
Early colonoscopy: Performance of prepared colonoscopy within 24 h of arrival | 79 |
| Elective Colonoscopy Performance of prepared colonoscopy between 24 and 96 h after arrival
Elective colonoscopy: Performance of prepared colonoscopy between 24 and 96 h after arrival | 80 |
| Total | 159 |
Baseline characteristics
| Characteristic | Total | Early Colonoscopy | Elective Colonoscopy |
|---|---|---|---|
| Age, Continuous | 70.3 years STANDARD_DEVIATION 12.6 | 68.8 years STANDARD_DEVIATION 12.8 | 71.9 years STANDARD_DEVIATION 12.3 |
| Bleeding source Colonic ulcer | 2 participants | 0 participants | 2 participants |
| Bleeding source Colorectal cancer | 5 participants | 3 participants | 2 participants |
| Bleeding source Diverticular bleeding (definite) | 26 participants | 10 participants | 16 participants |
| Bleeding source Diverticular bleeding (presumptive) | 73 participants | 37 participants | 36 participants |
| Bleeding source Hemorrhoid | 3 participants | 1 participants | 2 participants |
| Bleeding source Infectious colitis | 1 participants | 1 participants | 0 participants |
| Bleeding source Ischemic colitis | 14 participants | 9 participants | 5 participants |
| Bleeding source Other | 11 participants | 7 participants | 4 participants |
| Bleeding source Radiation colitis | 1 participants | 1 participants | 0 participants |
| Bleeding source Unknown | 26 participants | 13 participants | 13 participants |
| Bleeding source Upper GI bleeding | 1 participants | 0 participants | 1 participants |
| Body mass index | 23.5 kg/m^2 STANDARD_DEVIATION 3.7 | 23.0 kg/m^2 STANDARD_DEVIATION 3.3 | 23.9 kg/m^2 STANDARD_DEVIATION 4.1 |
| Cecal insertion | 154 Participants | 77 Participants | 77 Participants |
| Cecal insertion time | 9.3 minutes STANDARD_DEVIATION 6.5 | 9.6 minutes STANDARD_DEVIATION 19.2 | 9.0 minutes STANDARD_DEVIATION 6.5 |
| Cerebrovascular disease | 26 Participants | 11 Participants | 15 Participants |
| Chronic heart failure | 9 Participants | 4 Participants | 5 Participants |
| Chronic kidney disease | 19 Participants | 8 Participants | 11 Participants |
| Chronic obstructive pulmonary disease | 3 Participants | 3 Participants | 0 Participants |
| Cilostazol | 7 Participants | 5 Participants | 2 Participants |
| Collagen disease | 9 Participants | 4 Participants | 5 Participants |
| Dementia | 2 Participants | 0 Participants | 2 Participants |
| Diabetes mellitus | 27 Participants | 11 Participants | 16 Participants |
| Direct oral anticoagulants | 10 Participants | 3 Participants | 7 Participants |
| Expert endoscopist | 96 Participants | 48 Participants | 48 Participants |
| Hemodynamic instability | 5 Participants | 4 Participants | 1 Participants |
| Hemoglobin | 11.3 g/dL STANDARD_DEVIATION 2.5 | 11.4 g/dL STANDARD_DEVIATION 2.7 | 11.3 g/dL STANDARD_DEVIATION 2.3 |
| Ischemic heart disease | 30 Participants | 12 Participants | 18 Participants |
| Leukemia | 1 Participants | 0 Participants | 1 Participants |
| Liver cirrhosis | 3 Participants | 1 Participants | 2 Participants |
| Low-dose aspirin | 38 Participants | 16 Participants | 22 Participants |
| Malignant lymphoma | 2 Participants | 2 Participants | 0 Participants |
| NSAIDs | 30 Participants | 14 Participants | 16 Participants |
| Other antiplatelet drugs | 8 Participants | 5 Participants | 3 Participants |
| Peptic ulcer | 8 Participants | 6 Participants | 2 Participants |
| Previous lower GI bleeding | 58 Participants | 28 Participants | 30 Participants |
| Race/Ethnicity, Customized Asian | 159 Participants | 79 Participants | 80 Participants |
| Sex: Female, Male Female | 53 Participants | 27 Participants | 26 Participants |
| Sex: Female, Male Male | 106 Participants | 52 Participants | 54 Participants |
| Solid cancer | 19 Participants | 7 Participants | 12 Participants |
| Thienopyridine | 13 Participants | 7 Participants | 6 Participants |
| Total procedure time | 33.6 minutes STANDARD_DEVIATION 17.4 | 35.8 minutes STANDARD_DEVIATION 19.2 | 31.3 minutes STANDARD_DEVIATION 15.1 |
| Upper GI endoscopy before colonoscopy | 3 Participants | 2 Participants | 1 Participants |
| Warfarin | 10 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 79 | 0 / 80 |
| other Total, other adverse events | 9 / 79 | 8 / 80 |
| serious Total, serious adverse events | 2 / 79 | 0 / 80 |
Outcome results
Primary
Stigmata of Recent Hemorrhage (SRH) Identification Rate
Stigmata of Recent Hemorrhage (SRH) based on colonoscopic visualization of lesions, such as diverticulosis, tumor, ulcer, hemorrhoid, angioectasia, and polyps exhibiting active bleeding, a visible vessel, or an adherent clot.
Time frame: 0-4 day
Population: The primary analysis included a modified intention-to-treat population, excluding the following patients from the genuine intention-to-treat analysis set: 1) those who did not satisfy the enrollment criteria after randomization; 2) those who provided no post-randomization data on primary outcome; and 3) those who did not undergo colonoscopy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Colonoscopy | Stigmata of Recent Hemorrhage (SRH) Identification Rate | 17 Participants |
| Elective Colonoscopy | Stigmata of Recent Hemorrhage (SRH) Identification Rate | 17 Participants |
Secondary
Length of Stay
It will be defined as length of stay to cure acute lower gastrointestinal bleeding.
Time frame: 0-34 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early Colonoscopy | Length of Stay | 7.1 days | Standard Deviation 5.7 |
| Elective Colonoscopy | Length of Stay | 7.6 days | Standard Deviation 6 |
Secondary
Need for Additional Endoscopic Examinations
Additional endoscopic examinations will be defined as examinations to achieve hemostasis.
Time frame: 0-34 day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Colonoscopy | Need for Additional Endoscopic Examinations | 31 Participants |
| Elective Colonoscopy | Need for Additional Endoscopic Examinations | 23 Participants |
Secondary
Need for Interventional Radiology
It will be defined as radiology intervention to achieve hemostasis.
Time frame: 0-34 day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Colonoscopy | Need for Interventional Radiology | 1 Participants |
| Elective Colonoscopy | Need for Interventional Radiology | 0 Participants |
Secondary
Need for Surgery
It will be defined as surgery to achieve hemostasis.
Time frame: 0-34 day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Colonoscopy | Need for Surgery | 0 Participants |
| Elective Colonoscopy | Need for Surgery | 0 Participants |
Secondary
Need for Transfusion During Hospitalization
It will be defined as the numbers of patients who will need transfusion.
Time frame: During hospitalization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Colonoscopy | Need for Transfusion During Hospitalization | 30 Participants |
| Elective Colonoscopy | Need for Transfusion During Hospitalization | 26 Participants |
Secondary
Number of Participants With Colonoscopy-related Adverse Events
Colonoscopy-related adverse events will include hemorrhagic shock, and perforation.
Time frame: 0-4 day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Colonoscopy | Number of Participants With Colonoscopy-related Adverse Events | 1 Participants |
| Elective Colonoscopy | Number of Participants With Colonoscopy-related Adverse Events | 0 Participants |
Secondary
Number of Participants With Preparation-related Adverse Events
Preparation-related adverse events will include nausea, vomiting, abdominal pain, volume overload, aspiration pneumonia, hemorrhagic shock, exacerbation bleeding, and ileus
Time frame: 0-4 day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Colonoscopy | Number of Participants With Preparation-related Adverse Events | 36 Participants |
| Elective Colonoscopy | Number of Participants With Preparation-related Adverse Events | 28 Participants |
Secondary
Number of Participants With Thirty-day Death Events
Number of Participants with Thirty-day death Events from enrollment
Time frame: 30 day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Colonoscopy | Number of Participants With Thirty-day Death Events | 0 Participants |
| Elective Colonoscopy | Number of Participants With Thirty-day Death Events | 0 Participants |
Secondary
Number of Participants With Thirty-day Thrombosis Events
Thrombosis events will include acute coronary syndromes, including angina pectoris and myocardial infarction, stroke, including cerebrovascular infarction, cerebral hemorrhage, and transient ischemic attacks, deep vein thrombosis, and pulmonary embolism.
Time frame: 30 day
Population: Rebleeding,thrombotic events, and mortality were evaluated for patients who approximately met the 30-day follow-up criteria (early colonoscopy for 72 patients and elective colonoscopy for 75 patients).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Colonoscopy | Number of Participants With Thirty-day Thrombosis Events | 1 Participants |
| Elective Colonoscopy | Number of Participants With Thirty-day Thrombosis Events | 0 Participants |
Secondary
Success Rate of Endoscopic Treatment; Number of Participants Achieving Hemostasis With Endoscopic Treatment
Success rate will be defined as the number achieving hemostasis per total number of attempts at endoscopic hemostasis during colonoscopy examination.
Time frame: 0-4 day
Population: Success rate of endoscopic treatment was defined as achievement of hemostasis (early for 15 patients and elective for 15 patients).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Colonoscopy | Success Rate of Endoscopic Treatment; Number of Participants Achieving Hemostasis With Endoscopic Treatment | 14 Participants |
| Elective Colonoscopy | Success Rate of Endoscopic Treatment; Number of Participants Achieving Hemostasis With Endoscopic Treatment | 15 Participants |
Secondary
Thirty-day Rebleeding Rates
Rebleeding will be defined as significant fresh blood loss after an initial colonoscopy with any of the following criteria: i) Hemorrhagic shock, including cold sweat, nausea, syncope, or systolic blood pressure ≤ 90 mmHg. ii) Need for transfusion, according to the guidelines of the Ministry of Health, Labour, and Welfare. iii) Further colonoscopy identifies blood pooling, or iv) SRH in the lower gastrointestinal tract. v) Contrast-enhanced CT identifies extravasation in the colorectal region. However, these examinations will not be performed routinely if rebleeding occurs in the study period.
Time frame: 30 day
Population: Rebleeding,thrombotic events, and mortality were evaluated for patients who approximately met the 30-day follow-up criteria (early colonoscopy for 72 patients and elective colonoscopy for 75 patients).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Colonoscopy | Thirty-day Rebleeding Rates | 11 Participants |
| Elective Colonoscopy | Thirty-day Rebleeding Rates | 5 Participants |