Prospective observational study to evaluate the safety of extended use of P-CAB: Safety surveillance phase for PROTECT-HBR trial
- Conditions
- Diseases of the digestive system
- Registration Number
- KCT0005996
- Lead Sponsor
- Asan Medical Center
- Brief Summary
This clinical study was conducted to verify the safety of potassium competitive gastric acid secretion inhibitors for gastrointestinal protection in the group of high-risk patients with gastrointestinal bleeding under antithrombotic treatment. A total of 330 patients were registered and a prospective observational study was conducted, and the safety evaluation variables of the test drug were measured and compared. As a result, liver function abnormalities and gastrointestinal infections set as the primary safety variable were not observed, and hypergastrinemia was observed in 12 cases, in about 4% of all patients. Through this, it was confirmed that there was no significant abnormality in safety by using potassium competitive gastric acid secretion inhibitors, and there was no significant association with the test drug even in secondary safety variables and significant harmful cases. In addition, in the laboratory results observed while taking the drug, there was no significant change in the basal level and liver after taking the drug. Through this, it is believed that long-term safety of more than 6 months was proven when potassium competitive gastric acid secretion inhibitor (Tegoprazan 50mg) was administered in patients with high risk of digestive system bleeding receiving antithrombotic treatment. Based on this, it is expected that a randomized clinical study comparing existing proton pump inhibitors with potassium competitive gastric acid secretion inhibitors can be conducted in patients with high risk of gastrointestinal bleeding.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 330
Inclusion Criteria :
1. Patients 19 years of age or older with known cardiovascular disease in whom a requirement for chronic use of antithrombotic therapy (either antiplatelets or OAC). Specific clinical conditions that may confer a need for long-term antithrombotic therapy may include acute coronary syndrome and those with a history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, peripheral arterial disease, or atrial fibrillation. Concomitant use of a proton pump inhibitor is recommended in patients receiving aspirin monotherapy, DAPT (dual antiplatelet therapy), DAT (dual antithrombotic therapy), TAT (triple antithrombotic therapy.), or OAC monotherapy who are at high risk of gastrointestinal bleeding in order to reduce the risk of gastric bleeds (6,7,10).
2. On the basis of clinical guidelines (6,7,10,14-16) and expert consensus documents (17-19), we defined study population with increased risk of gastrointestinal bleeding if they had a least 1 or more criteria of the following characteristics. Eligible patients for randomization must meet at least 1 characteristics of these criteria:
*Definition of patients who are at high risk of gastrointestinal bleeding
a. Age =65 years
b. Concomitant use of OAC and any antiplatelet therapy (mono or DAPT) (i.e., DAT or TAT)
c. Long-term use of oral NSAIDs (non-steroidal anti-inflammatory drugs) or steroids or high dose NSAID therapy even during a relatively short-term period.
d. History of prior GI bleeding events at any time
e. History of a previously complicated ulcer
f. History of peptic ulcer disease or a previously uncomplicated ulcer
g. Documented Helicobacter pylori infection
3. 3.Patients who voluntarily participated in the written agreement
Exclusion Criteria :
1. Active bleeding at the time of inclusion or a history of hereditary or acquired hemostatic disorder
2. Previous chronic use of a PPI, P-CAB, H2 receptor blocker, sucralfate or misoprostol.
3. Any clinical contraindication to use of antithrombotic therapies (antiplatelet agents or OAC).
4. Hemodynamic unstable conditions at the time of inclusion: cardiogenic shock at the time of randomization, refractory ventricular arrhythmias, or congestive heart failure (New York Heart Association class IV).
5. Baseline severe anemia (Hgb <8 g/dl at baseline) or transfusion within 4 weeks before randomization
6. Baseline severe thrombocytopenia (platelet count <50,000/mm3)
7. Renal failure-dependent on dialysis or severe renal insufficiency (creatinine clearance <15 ml/min)
8. Severe chronic liver disease (defined as variceal hemorrhage, ascites, hepatic encephalopathy, or jaundice)
9. Hypersensitivity or contraindication to PPI, P-CAB, any of the product components, or substituted benzimidazoles
10. Systemic treatment with strong CYP 3A4 and p-glycoprotein (P-gp) inhibitors (e.g., systemic azole antimycotics, such as ketoconazole, and human immunodeficiency virus [HIV]-protease inhibitors, such as ritonavir)
11. Patients who take atazanavir, nelfinavir or rilpivirine-containing products (see Drug-Drug interaction section)
12. Clinically significant laboratory abnormality at screening (estimated glomerular filtration rate (eGFR) <15 mL/min or elevated liver enzyme [AST, ALT, ALP, total bilirubin] > 3 times upper normal limit [UNL] or any other condition that, in the opinion of the Investigator, precludes participation in the study
13. Any known or suspected malignancy
14. Subjects with non-cardiac co-morbidities with life expectancy less than 12 months
15. Women who are pregnant or breastfeeding or female subjects, premenopausal who are not surgically sterile, or, if sexually active not practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and, for those of childbearing potential, who have a positive pregnancy test at screening
16. Participation in another clinical study within 12 months
Study & Design
- Study Type
- Observational Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. liver function abnormalities;2. hypergastrinemia;3. enteric infection
- Secondary Outcome Measures
Name Time Method 1. Overt upper gastrointestinal bleeding (confirmed by means of upper endoscopy or CT);;2. Overt upper gastrointestinal bleeding of unknown origin;3. Bleeding of presumed occult gastrointestinal origin with documented decrease in hemoglobin of = 2 g/dL or decrease in hematocrit = 10% from baseline;;4. Symptomatic gastroduodenal ulcer (confirmed by means of endoscopy or CT) without evidence of gastrointestinal bleeding;;5. Persistent pain of presumed gastrointestinal origin (duration = 3 days) with underlying multiple erosive disease (5 or more gastroduodenal erosions confirmed by means of endoscopy);;6. Obstruction;;7. Perforation