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Proton Pump Inhibitor Preventing Upper Gastrointestinal Injury In Patients On Dual Antiplatelet Therapy After CABG (DACAB-GI-2)

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ClinicalTrials.gov Identifier: NCT03908593
Recruitment Status : Not yet recruiting
First Posted : April 9, 2019
Last Update Posted : April 9, 2019
Sponsor:
Information provided by (Responsible Party):
Lifen YU, Ruijin Hospital

Brief Summary:
The purpose of this study is to compare the efficacy of 12 months and 1 month of pantoprazole treatment to prevent upper gastrointestinal mucosal injury in patients on dual antiplatelet therapy (DAPT) after coronary artery bypass grafting (CABG).

Condition or disease Intervention/treatment Phase
Gastrointestinal Ulcer (Peptic) or Erosion Anti-Platelet Therapy Coronary Artery Bypass Drug: Pantoprazole Phase 4

Detailed Description:

A single-center, open-label, randomized controlled trial to compare the efficacy of 12 months and 1 month of pantoprazole treatment for the prevention of upper gastrointestinal mucosal injury in patients on DAPT after CABG. 13C urea breath testing (UBT) is used to detect Helicobacter pylori infection before CABG and 12 months after CABG, respectively. Esophagogastroduodenoscopy (EGD) is performed to evaluate the upper gastrointestinal mucosal injury at 6 and 12 months after CABG, respectively.

Two subgroup analyses will be performed in this study, including: (1) Helicobacter pylori infection: negative and positive; (2) DAPT: aspirin + clopidogrel and aspirin + ticagrelor.

To our knowledge, no published data or reference is available for the presence and severity of upper gastrointestinal mucosal injury evaluated by EGD in patients on DAPT (ticagrelor + aspirin). DACAB-GI-1 study, a single-center endoscopic observational study, was conducted with the DACAB randomized clinical trial (NCT 02201771, n=500). Briefly, patients aged 18 to 80 years with indications for elective CABG surgery were randomized to 1 year of open-label antiplatelet therapy comprised of ticagrelor (90 mg twice daily) + aspirin (100 mg once daily), ticagrelor alone (90 mg twice daily), or aspirin alone (100 mg once daily). Upper gastrointestinal mucosal lesions and use of PPIs were assessed in 231 patients enrolled in Ruijin Hospital at 1 year post-CABG. According to the results of DACAB-GI-1, the minimum sample size of this study is determined to be 208 cases.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 208 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Evaluation of the Efficacy of Different Duration of a Proton Pump Inhibitor in the Prevention of Upper Gastrointestinal Mucosal Injury in Patients Taking 12-month Dual Antiplatelet Therapy After Coronary Artery Bypass Grafting
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: One month of therapy
Pantoprazole, 40mg, tablet, oral, once daily for 1 month
Drug: Pantoprazole
Pantoprazole (40mg qd) will be concomitant used with DAPT
Other Name: PANTOLOC, Tablet from Takeda Pharmaceutical Company Limited

Experimental: Twelve months of therapy
Pantoprazole, 40mg, tablet, oral, once daily for 12 months
Drug: Pantoprazole
Pantoprazole (40mg qd) will be concomitant used with DAPT
Other Name: PANTOLOC, Tablet from Takeda Pharmaceutical Company Limited




Primary Outcome Measures :
  1. Percentage of patients with gastroduodenal erosions and ulcers evaluated by EGD. [ Time Frame: 12 months after randomization ]
    Gastroduodenal erosions and ulcers will be assessed according to the Lanza Endoscopic Scoring System. Lanza score is a categorical score (0-4) and defined as follows: 0, normal; 1, mucosal haemorrhages only; 2, 1-2 erosions; 3, 3-10 erosions; 4, >10 erosions or an ulcer ≥3 mm. In addition, ≥1 ulcer with a diameter ≥5mm will be grouped separately.


Secondary Outcome Measures :
  1. Percentage of patients with gastroduodenal erosions and ulcers evaluated by EGD. [ Time Frame: 6 months after randomization ]
    Gastroduodenal erosions and ulcers will be assessed according to the Lanza Endoscopic Scoring System (0-4). In addition, ≥1 ulcer with a diameter ≥5mm will be grouped separately.

  2. Cumulative number of patients with upper gastrointestinal bleeding (UGIB) according to the modified TIMI criteria. [ Time Frame: up to 12 months ]
    According to the definition of non-CABG related bleeding in the modified TIMI criteria, the severity of UGIB is classified into 3 grades: major, minor and minimal. 1, Major: Clinically overt signs of hemorrhage associated with a drop in hemoglobin of ≥5 g/dL. 2, Minor: Clinically overt signs of UGIB, resulting in hemoglobin drop of 3 to <5 g/dL. 3, Minimal: Any overt bleeding event that does not meet the criteria above. According to the consensus updated by the Asia-Pacific working group in 2018, patients with haemodynamic shock and signs of UGIB should be offered urgent endoscopy after resuscitation and stabilization (Gut 2018; 67:1757-68).

  3. Percentage of patients with reflux esophagitis evaluated by EGD. [ Time Frame: 12 months after randomization ]
    According to the Los Angeles classification, endoscopic reflux esophagitis was assigned a grade from A to D.

  4. Percentage of patients with reflux esophagitis evaluated by EGD. [ Time Frame: 6 months after randomization ]
    According to the Los Angeles classification, endoscopic reflux esophagitis was assigned a grade from A to D.


Other Outcome Measures:
  1. Cumulative number of patients with major adverse cardiovascular events (MACE). [ Time Frame: up to 12 months ]
    MACE: composite of cardiovascular death, myocardial infarctions, or stroke.

  2. The failure rate of grafts assessed by multislice computed tomographic angiography or coronary angiography. [ Time Frame: up to 12 months ]
    Graft failure: Stenosis ≥50% or occlusion of the graft or distal anastomosis.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Each patient should meet all of the inclusion criteria and none of the exclusion criteria for this study:

  1. Provision of signed informed consent prior to any study specific procedures.
  2. Male or female, age ≥ 18 years at the time of consent.
  3. Planned or initiated use of 12 months of DAPT (aspirin plus clopidogrel or aspirin plus ticagrelor) immediately following primary isolated elective CABG surgery.

Exclusion Criteria:

Patients should not enter the study if any of the following exclusion criteria are fulfilled.

  1. History of previous active peptic ulcer within 3 months prior to enrollment.
  2. Planned use of PPIs to treat acid-associated disorders (e.g. gastroesophageal reflux disease, GERD)
  3. Contraindications for aspirin, clopidogrel, ticagrelor and pantoprazole use (e.g. known allergy)
  4. Anticipated concomitant oral or intravenous therapy with strong cytochrome P450 3A4 (CYP3A4) inhibitors or CYP3A4 substrates with narrow therapeutic indices, that cannot be stopped for the course of the study.

    • Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir
    • CYP3A4 substrates with narrow therapeutic index: quinidine, simvastatin at doses > 40mg daily or lovastatin at doses > 40mg daily.
  5. Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin.
  6. Women of child-bearing potential who are not willing to use a medically accepted method of contraception that is considered reliable in the judgement of investigator OR women who have a positive pregnancy test at enrollment or randomization OR women who are breasting-feeding.
  7. Inability of patient to understand and/or comply with study procedures and/or follow up, in the opinion of the investigator, OR any conditions that, in the opinion of the investigator, many render the patient unable to complete the study.
  8. Any condition outside the atherothrombotic study area with a life expectancy of less than 1 year.
  9. Participation in another clinical study with an investigational product within 28 days prior to enrolment or previous randomization to an investigational product in another ongoing clinical study.
  10. Any condition which in the opinion of the investigator would make it unsafe or unsuitable for the patient to participate in this study (eg, long-term concomitant treatment with non-steroidal anti-inflammatory drugs [NSAIDs])

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03908593


Contacts
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Contact: Lifen Yu, MD, Ph.D 0086-13641937166 ylf10975@rjh.com.cn
Contact: Yunpeng Zhu, MD 0086-13816819346 zypB1014@rjh.com.cn

Locations
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China
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, China, 200025
Sponsors and Collaborators
Ruijin Hospital
Investigators
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Principal Investigator: Lifen Yu, MD, Ph.D Ruijin Hospital

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Responsible Party: Lifen YU, Associate Professor, Department of Gastroenterology, Ruijin Hospital
ClinicalTrials.gov Identifier: NCT03908593     History of Changes
Other Study ID Numbers: IISR-2016-101603 (RJ)
First Posted: April 9, 2019    Key Record Dates
Last Update Posted: April 9, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lifen YU, Ruijin Hospital:
Gastrointestinal
Mucosal injury
Antiplatelet
Coronary artery bypass grafting
Prevention

Additional relevant MeSH terms:
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Pantoprazole
Proton Pump Inhibitors
Anti-Ulcer Agents
Gastrointestinal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action