A Multi-center, Double-blinding, Parallel and Positive-controlled Phase III Clinical Trial for Efficacy and Safety Evaluation of Ilaprazole Sodium for Injection on Prevention of Stress Ulcer Bleeding

Livzon Pharmaceutical Group

Status and phase: Completed; Phase 3

Conditions: Stress Ulcer Bleeding

Treatments: Drug: Placebo 2; Drug: Ilaprazole Sodium; Drug: Esomeprazole 40mg; Drug: Placebo 1

Study type: Interventional

Funder types: Industry

Identifiers

NCT05841394

LZ1075

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy of the study drug (Ilaprazole Sodium for Injection) for potential effect on preventing stress ulcer bleeding in vulnerable population by comparing the radio of upper gastrointestinal bleeding when they are administered Ilaprazole Sodium for Injection and Esomeprazole Sodium for Injection respectively.

Enrollment: 449 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• voluntarily signed informed consent form by subjects per se or their guardians.

• 18-74 years of age, female or male;

• required by the ICU treatment, and is intended to be treated over 72 hours.

• intragastrically intubated for at least 72 hours;

• APACHE II scoring within 15 to 25 (containing upper and lower value)

• intubated by mechanical assistance for breath for intended 48 hours without permission of assistance withdrawal. (Combing clinical observation, patients judged cannot breathing without artificial assistance within 48 hours should meet the any of criteria as following: 1) PEEP > 5; 2) FiO2 > 0.4; 3) Pressure of assisting breathing machine > 13 cmH2O; 4) body temperature over 38℃; 5) CRP ≥ 100 mg/L.

• in addition to mechanical ventilation, at least one major factor that may lead to irritable ulcer bleeding occurred as following within 48 hours prior to random group-assignment.

  1. complex organ surgery at Level 3 or above (surgery duration > 3 hours);
  2. disease history of gastrointestinal ulcer or hemorrhage;
  3. multiple injuries (score (ISS) ≥ 16);
  4. shock
  5. multiple organ dysfunction syndrome (MODS);
  6. sepsis (as per definition of issued by the Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) in 2016)
  7. acidosis (arterial pH < 7.3);
  8. coagulation dysfunction (INR > 1.5, platelets < 50 * 109/L or APTT > 2 times normal value;
  9. coma (GCS ≤ 10);
  10. receiving high dose corticosteroids (over 250 mg/d hydrocortisone or other equivalent dose corticosteroids);
  11. 30%-70% body surface burn;

Exclusion criteria

• a history of gastric or esophageal surgery, intestinal obstruction, or hospitalization in the ICU after esophageal, gastric, or duodenal surgery in the past 3 months;
• lesions of the upper digestive tract (e.g., duodenal ulcer, gastric ulcer, acute gastric mucosa lesions, esophageal varices, malignant tumors, etc.) that are known to be likely to bleed, and other evidences indicating gastrointestinal bleeding occurs (esophageal and gastric varices bleeding, duodenal ulcer bleeding);
• hemoglobin < 60g/L (6.0g/dl);
• significant factor indicating bleed occurs during swallowing (such as oral and maxillofacial injuries, hemoptysis, etc.);
• renal failure;
• cardiopulmonary resuscitation conducted during hospitalization period;
• serious liver disease, defined as Child-Pugh C-grade;
• contraindicated for gastric intubation (such as esophageal stenosis);
• pregnancy or pregnancy test showing positive;
• documented or supposed to be hypersensitive to PPIs (Ilaprazole, Esomeprazole, Omeprazole, Lansoprazole, Dextran lansoprazole, Rabeprazole or Pantoprazole);
• participated in other clinical studies within 30 days prior to random assignment;
• use any PPI or treated by H2RA within 12 hours prior to random assignment;
• co-administering or unavoidable using drugs that may interact with Ilaprazole Sodium or Esomeprazole Sodium: e.g., Warfarin (including other vitamin K antagonists), Cisapride, Phenytoin, Atazanavir, Nefenavir, Ritonavir, Saquinavir, Digoxin, Tacrolimus, Methotrexate.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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449 participants in 2 patient groups

Esomeprazole Sodium

Active Comparator group

Description:

40 mg twice daily (q12h)

Treatment:

Drug: Esomeprazole 40mg

Drug: Placebo 2

Ilaprazole Sodium

Experimental group

Description:

10 mg once daily, 20 mg dosed in the first day.

Treatment:

Drug: Placebo 1

Drug: Ilaprazole Sodium