Fexuprazan for Prevention of Upper Gastrointestinal Bleeding in High Bleeding Risk Patients Receiving Dual Antiplatelet Therapy

Официальное название

Randomized Active-Controlled Trial Evaluating Fexuprazan for Prevention Upper Gastrointestinal Bleeding in High Bleeding Risk Patients Receiving Dual Antiplatelet Therapy After Coronary Intervention-Fexuprazan for Patients With Dual Antiplatelet Therapy Trial

Обзор

This study evaluates whether fexuprazan is effective in preventing upper gastrointestinal bleeding and related upper gastrointestinal clinical events in high bleeding risk patients who require dual antiplatelet therapy after coronary stent implantation. A total of 400 participants at a single center will be randomly assigned in a 1:1 ratio within 48 hours after stent implantation to receive either fexuprazan 40 milligrams or lansoprazole 30 milligrams once daily for 6 months. The study will compare upper gastrointestinal clinical events during follow-up

Подробное описание

The use of antiplatelet agents inevitably increases the risk of bleeding, which is associated with increased mortality. Gastrointestinal bleeding, including upper gastrointestinal bleeding, is the most common bleeding complication, accounting for approximately two-thirds of bleeding events associated with dual antiplatelet therapy (DAPT). The use of proton pump inhibitors (PPIs) has been investigated to reduce the risk of gastrointestinal bleeding, and the Clopidogrel and the Optimization of Gastrointestinal Events Trial (COGENT) was the only large study to report a reduction in gastrointestinal bleeding with PPI use. However, smaller randomized trials and meta-analyses have reported conflicting results regarding the efficacy of PPI use. In addition, PPIs require caution when used in conjunction with P2Y12 inhibitors such as clopidogrel, as they may reduce antiplatelet activity and increase the risk of thrombotic events.

Currently, European clinical guidelines recommend prescribing PPIs as gastrointestinal protective agents to all patients, whereas American College of Cardiology Foundation, American College of Cardiology, and American Heart Association (ACCF/ACC/AHA) clinical guidelines recommend prescribing PPIs only to patients at high risk of upper gastrointestinal bleeding rather than universal use. With an increase in coronary stenting among elderly and high-risk patients with coronary artery disease, the population at high risk of bleeding is also increasing. Approximately 20 percent of patients were identified as being at high risk of bleeding within 1 year after coronary artery intervention according to Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding criteria. Additionally, East Asians, including Koreans, are known to be at higher risk of upper gastrointestinal bleeding because of various genetic and environmental factors. Therefore, efforts to prevent gastrointestinal bleeding during the period of DAPT after stent insertion are increasingly important.

Potassium-competitive acid blockers (P-CABs) are a new class of hydrogen/potassium adenosine triphosphatase (H+/K+ ATPase) inhibitors used to treat gastrointestinal acid-related disorders such as gastroesophageal reflux disease, peptic ulcers, and Helicobacter pylori infections. Unlike PPIs, which bind to the proton pump, P-CABs competitively and reversibly inhibit the potassium site of H+/K+ ATPase, leading to relatively long-lasting inhibition of acid secretion. Fexuprazan (Fexuclue) has demonstrated efficacy in phase 3 clinical trials in patients with erosive esophagitis and has been shown to have a faster onset of action than esomeprazole and sustained acid suppression throughout the night. Therefore, this double-blind, randomized, active-controlled study was designed to evaluate the preventive effect of fexuprazan on upper gastrointestinal events in high-risk patients who require DAPT.

A total of 400 participants at a single center will be enrolled. Eligible participants will be randomly assigned in a 1:1 ratio within 48 hours after stent implantation to receive either fexuprazan 40 milligrams or lansoprazole 30 milligrams

Вмешательства

• Препарат Fexuprazan 40mg
  Fexuprazan 40 mg orally once daily + Lansoprazole placebo Matching placebo orally once daily.
• Препарат Lansoprazole 30mg
  Lansoprazole 30 mg orally once daily. + Fexuprazan placebo Matching placebo orally once daily.

Первичные конечные точки

• Time from randomization to first occurrence of a composite endpoint of upper gastrointestinal clinical events during the treatment period [Срок оценки: 6 months after randomization]

Вторичные конечные точки (10)

• Time from randomization to first occurrence of gastroesophageal reflux disease, as evidenced by symptomatic endoscopically-confirmed erosive esophagitis. [Срок оценки: 6 months after randomization]
• Time from randomization of first occurrence of low gastrointestinal bleeding (conformed by the endoscopy or CT scan) [Срок оценки: 6 months after randomization]
• Time from randomization to first occurrence of any GI bleeding [Срок оценки: 6 months after randomization]
• BARC bleeding (BARC type 0, 1, 2, 3, 5) [Срок оценки: 6 months after randomization]
• All-cause death (cardiovascular death, or non-cardiovascular death) [Срок оценки: 6 months after randomization]
• Rate of participants with myocardial infarction (target-vessel or non-target-vessel) [Срок оценки: 6 months after randomization]
• Rate of participants who underwent coronary revascularization (target-vessel or non-target-vessel) [Срок оценки: 6 months after randomization]
• Rate of participants with stent thrombosis [Срок оценки: 6 months after randomization]
• Rate of participants with stroke (ischemic, hemorrhagic, or transient ischemic attack) [Срок оценки: 6 months after randomization]
• Change in Dyspepsia-Related Health Assessed by the Severity of Dyspepsia Assessment (SODA) Questionnaire [Срок оценки: 6 months after randomization]

Критерии участия

Критерии включения

• All four conditions below must be met.

• Patients who are 20 years of age or older, have undergone coronary artery stent implantation for coronary artery disease, and require dual antiplatelet therapy for 6 months or longer.
• Patients are considered to be at high bleeding risk if at least 1 criteria are met (Based on clinical recommendations (6,7,10,14-16) and expert consensus documents (17-19)) 1) Age ≥65 y 2) Low body weight (<55 Kg for men, <50 Kg for women) 3)Hemoglobin <11g/dL 4) Platelet count <100×109/L 5) Severe CKD: eGFR <30mL/min/1.73m2,5 or on hemodialysis 6) Anticipated use of long-term oral anticoagulation (warfarin or direct-acting oral anticoagulants) 7) Long-term use of oral NSAIDs or steroids 8) Heart failure 9) A history of previous gastric or duodenal ulcer. 10) A history of previous gastrointestinal bleeding. 11)Previous or confirmed Helicobacter pylori infection
• A voluntary participant in this clinical trial who has provided written consent, or a legal guardian who has provided written consent on behalf of the participant.
• Those who agree to use a medically valid method of contraception\* (including conditions in which pregnancy is medically impossible) during the clinical trial period Women who are medically unable to become pregnant can participate in this clinical trial: women who have undergone menopause (amenorrhea for more than 24 months), hysterectomy, salpingectomy, or bilateral oophorectomy, etc.
• Medically valid contraceptive methods: intrauterine device (Loop, Mirena), physical barrier method (male condom, female condom (femidom)), subcutaneous contraception (Implanon, etc.), long-acting contraceptive injection, or tubectomy and ligation, vasectomy, etc. ( However, oral contraceptives cannot be used during this clinical trial, and it is recommended to use double contraception to prevent pregnancy while participating in this trial.)

Критерии исключения

• Patients who have a hypersensitivity reaction to the components of this clinical trial drug or benzimidazole-based drugs or have a history of clinically significant hypersensitivity reaction
• Patients with contraindications to antiplatelet agents, such as allergies.
• Genetic blood coagulation disorders
• Cases in which the investigator determines that the use of dual antiplatelet therapy is difficult due to severe liver cirrhosis, thrombocytopenia, or other medical conditions.
• Hemodynamically unstable at the time of randomization (cardiogenic shock, uncontrolled arrhythmia, severe heart failure: NYHA Class IV).
• Patients with warning symptoms suspected of digestive malignancy (unintentional significant weight loss, recurrent vomiting, dysphagia, hematemesis, melena, etc.) within the past 3 months
• Patients with malignancy or serious illnesses with an expected survival of less than 1 year.
• Severe anemia (hemoglobin < 8 g/dL) or blood transfusion within 4 weeks of randomization.
• Active liver disease or impaired liver function (AST or ALT greater than three times the upper limit of normal).
• Advanced renal dysfunction: eGFR less than 30 mLmin/1.73m2 or patients receiving dialysis
• Patients taking drugs contraindicated for this clinical trial drug (e.g., patients taking atazanavir, nelfinavir, or rilpivirine-containing preparations)
• Patients with genetic problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
• Concurrently taking CYP 3A4 and p-glycoprotein (P-GP) inhibitors.
• Dementia or individuals unable to understand the trial procedures or comply with the trial requirements
• Pregnant or breastfeeding women, or women planning to become pregnant
• Individuals with active infections, significant hematologic, renal, metabolic, gastrointestinal, endocrine disorders, or any other reason the investigator deems the subject unsuitable for participation in the clinical trial

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

South Korea · 1 центр

• The Catholic University of Korea, Eunpyeong St. Mary's Hospital — Seoul

Публикации

• Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, Normand SL, Braunwald E, Wiviott SD, Cohen DJ, Holmes DR Jr, Krucoff MW, Hermiller J, Dauerman HL, Simon DI, Kandzari DE, Garratt KN, Lee DP, Pow TK, Ver Lee P, Rinaldi MJ, Massaro JM; DAPT Study Investigators. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014 Dec 4;371(23):2155-66. d PMID 25399658
• Niteen V. Deshpande; Bleeding on dual antiplatelet therapy: real-life challenges; European Heart Journal Supplements; 2018; 20 (Supplement B); B1-B9

Идентификаторы

NCT: NCT07479056 · PC24MIST0009 · KCT0009504

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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