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Mono- Versus Dual antiPlatelet Therapy During 6-12 Months After New Generation Drug Eluting Stent Implantation (OPT-PEACE)

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ClinicalTrials.gov Identifier: NCT03198741
Recruitment Status : Recruiting
First Posted : June 26, 2017
Last Update Posted : May 9, 2018
Sponsor:
Collaborators:
Changhai Hospital
ANKON medical technologies (Shanghai)Co.,LTD
Information provided by (Responsible Party):
Han Yaling, Shenyang Northern Hospital

Tracking Information
First Submitted Date  ICMJE June 19, 2017
First Posted Date  ICMJE June 26, 2017
Last Update Posted Date May 9, 2018
Actual Study Start Date  ICMJE July 14, 2017
Estimated Primary Completion Date December 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2017)
Gastrointestinal mucosal Injury (erosion, ulceration or bleeding) [ Time Frame: 12 months after enrollment (i.e. 6 months after randomization) ]
Detected by AMCE
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03198741 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2017)
  • The severity of gastric and intestinal mucosal lesions [ Time Frame: During the first 6 months after study enrollment (prior to randomization) ]
    Detected by AMCE and calculated with a score system
  • The severity of gastric and intestinal mucosal lesions [ Time Frame: After randomization (i.e. between 6 months and 12 months after study enrollment) ]
    Detected by AMCE and calculated with a score system
  • Clinical indicated bleeding of the upper gastrointestinal tract [ Time Frame: During 6 months after study enrollment (prior to randomization) ]
    1. Hematemesis is defined as vomiting of blood or blood clots, and generally indicates bleeding of the upper gastrointestinal tract.
    2. Hematochezia is the passage of fresh blood per anus, usually in or with stools, and typically signifies lower GI tract bleeding.
    3. Melena is the passage of black, tarry stool and typically signifies upper tract GI bleeding.
    4. The positive fecal occult blood refers to blood in the feces that is not visibly apparent (unlike other types of blood in stool such as melena or hematochezia).
  • Clinical indicated evident gastrointestinal hemorrhage [ Time Frame: After randomization (i.e. between 6 months and 12 months after study enrollment) ]
    1. Hematemesis is defined as vomiting of blood or blood clots, and generally indicates bleeding of the upper gastrointestinal tract.
    2. Hematochezia is the passage of fresh blood per anus, usually in or with stools, and typically signifies lower GI tract bleeding.
    3. Melena is the passage of black, tarry stool and typically signifies upper tract GI bleeding.
    4. The positive fecal occult blood refers to blood in the feces that is not visibly apparent (unlike other types of blood in stool such as melena or hematochezia).
  • Clinical indicated gastrointestinal hemorrhage [ Time Frame: 12 months after enrollment (i.e. 6 months after randomization) ]
    1. Hematemesis is defined as vomiting of blood or blood clots, and generally indicates bleeding of the upper gastrointestinal tract.
    2. Hematochezia is the passage of fresh blood per anus, usually in or with stools, and typically signifies lower GI tract bleeding.
    3. Melena is the passage of black, tarry stool and typically signifies upper tract GI bleeding.
    4. The positive fecal occult blood refers to blood in the feces that is not visibly apparent (unlike other types of blood in stool such as melena or hematochezia).
  • Gastrointestinal symptoms [ Time Frame: 12 months after enrollment (i.e. 6 months after randomization) ]
    pain, nausea/vomiting, dysphagia, other discomfort
  • All bleeding [ Time Frame: 12 months after enrollment (i.e. 6 months after randomization) ]
    BARC types 1-5
  • Target lesion failure [ Time Frame: 12 months after enrollment (i.e. 6 months after randomization) ]
    TLF: cardiac death, target-vessel MI, or clinically-driven target lesion revascularization
  • Net adverse clinical events [ Time Frame: 12 months after enrollment (i.e. 6 months after randomization) ]
    NACE, defined as TLF or BARC type 2-5 bleeding
  • Stent thrombosis [ Time Frame: 12 months after enrollment (i.e. 6 months after randomization) ]
    ARC definite, probable, or definite/probable
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mono- Versus Dual antiPlatelet Therapy During 6-12 Months After New Generation Drug Eluting Stent Implantation
Official Title  ICMJE COmparison of Mono- Versus Dual antiPlatelet Therapy During 6-12 Months After New Generation Drug Eluting Stent Implantation for Prevention of Gastrointestinal Injury Evaluated by Ankon Magnetically Controlled Capsule Endoscopy
Brief Summary Long-term DAPT is recommended after percutaneous coronary intervention (PCI) in patients with coronary artery disease. However, antiplatelet therapy may have adverse consequences, the most common of which is gastrointestinal mucosal injury with ulceration and bleeding. The extent to which an an abbreviated DAPT strategy reduces gastrointestinal mucosal injury has not been studied, principally due to the lack of sensitive, noninvasive measurements capable of detecting gastrointestinal injury.ANKON® magnetically controlled capsule endoscopy (AMCE) is a non-invasive, active controlled system which affords assessment of the stomach and entire small intestine.The current randomized study will assess gastrointestinal mucosal injury and bleeding via AMCE in patients on three different antiplatelet regimens and establish a gastrointestinal mucosal injury scoring system which may prove useful in guiding optimal antiplatelet agent usage after PCI.
Detailed Description

Dual antiplatelet therapy (DAPT) with aspirin and a platelet P2Y12 receptor inhibitor has become the cornerstone for secondary prevention of coronary artery disease. Long-term DAPT is recommended after percutaneous coronary intervention (PCI) in patients with coronary artery disease to prevent future thrombotic events arising from the stent or untreated coronary lesions. However, antiplatelet therapy may have adverse consequences, the most common of which is gastrointestinal mucosal injury with ulceration and bleeding. The frequency of gastrointestinal complications increases with the duration of DAPT. Studies in patients treated with current generation drug-eluting stents have demonstrated that shortened DAPT regimens reduce the risk of bleeding events with small ischemic risk. However, the optimal duration of DAPT is still controversial. The extent to which an an abbreviated DAPT strategy reduces gastrointestinal mucosal injury has not been studied, principally due to the lack of sensitive, noninvasive measurements capable of detecting gastrointestinal injury.

Endoscopic examination of the gastric mucosa (gastroscopy) has high sensitivity and accuracy to detect gastrointestinal injury and bleeding. However, endoscopy is invasive and thus has no role in screening for sub-clinical gastrointestinal bleeding in patients undergoing PCI. Rather, endoscopy examinations are reserved for patients with active bleeding to identify the location of origin and etiology of the bleed. Moreover, gastroenterologists often refuse to perform gastroscopy in patients on DAPT given the risk of iatrogenic trauma with excessive hemorrhage. To minimize this risk, one or both antiplatelet agents often have to be discontinued for several days prior to the procedure, delaying the diagnosis while increasing the risk of stent thrombosis. Finally, upper endoscopy can only detect pathology related to the stomach and duodenum, as it does not visualize the remainder of the small intestine.

ANKON® magnetically controlled capsule endoscopy (AMCE) is a non-invasive, active controlled system which affords assessment of the stomach and entire small intestine. In the AMCE procedure, the patient swallows a capsule containing an endoscope which is actively maneuvered via magnetic control in the stomach, and then passes through the gastrointestinal track until its ultimate excretion. AMCE has several advantages compared to standard endoscopy. AMCE is noninvasive, painless and convenient, and can be re-administered as necessary. Patient acceptance of AMCE is likely to be substantially higher than standard endoscopy as the procedure involves only swallowing a capsule endoscope, without anesthesia or recovery time. Compared to standard endoscopy, AMCE provides more comprehensive detection of gastrointestinal pathology as it visualizes not only the stomach and duodenum, but the entire small intestine. Finally, discontinuation of antiplatelet drugs during AMCE is not necessary. Because of these advantages, AMCE can be used for screening of gastrointestinal mucosal lesions prior to clinical bleeding, including early detection of small areas of focal and concealed bleeding. Detection of preclinical gastric ulcerations or bleeding may be useful in directing preventative measures, whether gastro-protective therapies or DAPT discontinuation. A large-scale, randomized trial has confirmed that the sensitivity and specificity of AMCE for the detection of focal lesions of the gastrointestinal tract is similar to standard endoscopy. However, the potential utility of AMCE in patients receiving antiplatelet therapy after PCI has not been reported.

The current randomized study will evaluate AMCE as a tool to assess gastrointestinal mucosal injury and bleeding in patients on DAPT; evaluate the relative rates of gastrointestinal injury in patients on three different antiplatelet regimens; and establish a gastrointestinal mucosal injury scoring system which may prove useful in guiding optimal antiplatelet agent usage after PCI.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Gastrointestinal Injury
  • Ischemic Heart Disease
Intervention  ICMJE
  • Drug: Aspirin + clopidogrel
    After randomization(6 months±2 weeks after enrollment),receive aspirin 100mg/d + clopidogrel 75mg/d for an additional 6 months. The above treatments between 6 and 12 months are double-blinded.
  • Drug: Clopidogrel monotherapy
    After randomization(6 months±2 weeks after enrollment),receive clopidogrel 75mg/d + placebo (clopidogrel monotherapy group) for an additional 6 months. The above treatments between 6 and 12 months are double-blinded.
    Other Name: Clopidogrel + placebo
  • Drug: Aspirin monotherapy
    After randomization(6 months±2 weeks after enrollment),receive aspirin 100mg/d + placebo (aspirin monotherapy group) for an additional 6 months. The above treatments between 6 and 12 months are double-blinded.
    Other Name: Aspirin + clopidogrel
Study Arms  ICMJE
  • Active Comparator: Aspirin+clopidogrel

    Open label clopidogrel (75mg/d) plus aspirin (100mg/d) for first 6 months after enrollment. At 6 months (±2 weeks),continue aspirin + clopidogrel (12-month DAPT group).The treatments between 6 and 12 months are double-blinded.

    Evaluation of gastric and intestinal mucosal lesions by AMCE will be performed at the time of screening, randomization (at 6 months ±2 weeks) and 6 months thereafter (at 12 months ±2 weeks).

    Intervention: Drug: Aspirin + clopidogrel
  • Experimental: Aspirin

    Open label clopidogrel (75mg/d) plus aspirin (100mg/d) for first 6 months after enrollment. At 6 months (±2 weeks),receive aspirin + placebo (aspirin monotherapy group) for an additional 6 months. The above treatments between 6 and 12 months are double-blinded.

    Evaluation of gastric and intestinal mucosal lesions by AMCE will be performed at the time of screening, randomization (at 6 months ±2 weeks) and 6 months thereafter (at 12 months ±2 weeks).

    Intervention: Drug: Aspirin monotherapy
  • Experimental: Clopidogrel

    Open label clopidogrel (75mg/d) plus aspirin (100mg/d) for first 6 months after enrollment. At 6 months (±2 weeks),receive clopidogrel + placebo (clopidogrel monotherapy group) for an additional 6 months. The above treatments between 6 and 12 months are double-blinded.

    Evaluation of gastric and intestinal mucosal lesions by AMCE will be performed at the time of screening, randomization (at 6 months ±2 weeks) and 6 months thereafter (at 12 months ±2 weeks).

    Intervention: Drug: Clopidogrel monotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 22, 2017)
593
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2019
Estimated Primary Completion Date December 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Adult patients with age of 18-80 years;
  2. Presentation with silent ischemia, stable angina, or non-ST-segment elevation acute coronary syndrome with GRACE score <140 on admission;
  3. PCI only with implantation of current generation drug-eluting stent(s) for coronary artery disease during the present admission [current generation DES refers to DES with thin cobalt-chromium or platinum-chromium struts, with a durable or biodegradable polymer eluting a rapamycin-analogue antiproliferative agent. The current major DES available in China market include: EXCEL and EXCEL 2 (JW Medical System, Weihai, China), Tivoli(Essen Technology, Beijing, China), Endeavor Resolute (Medtronic Inc., Minnesota, USA), FireHawk (MicroPort Medical (Group) Co., Ltd, Shanghai, China), BuMA (SinoMedical,China),Xience V (Abbott Laboratories, Abbott Park, Illinois, USA), Xience Prime (Abbott Laboratories, Abbott Park, Illinois, USA), Promus Element and Synergy (BostonTechnologies, Massachusetts, USA)].
  4. PCI resulted in complete revascularization (successful PCI treatment of all epicardial coronary lesions with diameter stenosis >70% or intermediate lesions with FFR ≤0.80);
  5. Intended treatment with dual antiplatelet therapy (aspirin + clopidogrel) after the DES procedure for at least 6 months;
  6. Agreement to comply with all study procedures.
  7. Written informed consent provided.

Exclusion Criteria:

  1. Presentation with STEMI;
  2. Left main disease (diameter stenosis >30% );
  3. Any prior coronary stent implantation during the last year prior to the index procedure;
  4. Implantation of of first-generation drug-eluting stents or bioabsorbable scaffolds during the index procedure;
  5. Implantation of >4 stents during the index procedure;
  6. Any prior stent thrombosis;
  7. Any active gastrointestinal bleeding or ulcers, or prior gastrointestinal bleeding or ulcers within the last 24 months;
  8. Prior gastrointestinal tract or abdominal surgery other than simple procedures which would not change the gastrointestinal tract anatomy, such as polyp removal, cholecystectomy or appendectomy;
  9. Contraindications to the AMCE test, including suspected or known gastrointestinal obstruction, stenosis, fistula, diverticula, etc.; presence of gastrointestinal obstruction symptoms such as pain or dysphagia; inoperative conditions or refusal to undergo abdominal surgery if required (i.e, if the capsule will not pass and cannot be removed by endoscopy)
  10. Severe hemorrhoids (phase 3-4 according to guidelines of American Society of Colon and Rectal Surgery);
  11. LVEF <0.40 on admission according to cardiac ultrasound;
  12. Renal dysfunction (eGFR <30ml/min/1.73m2);
  13. Active hepatitis or ALT >3 times upper limits of normal on admission;
  14. Uncontrolled severe hypertension (>180/110mmHg);
  15. Hemoglobin <100 g/L;
  16. Platelet count <100×109/L;
  17. Planned use of a proton pump inhibitor, gastric mucosa protectant or any other antacid agent after study enrollment;
  18. Required use of oral anticoagulation (warfarin or other factor II or factor X inhibitors);
  19. Inability to take 12-month DAPT for any reason;
  20. Mandatory use of >6 month DAPT (i.e. contraindication to aspirin or clopidogrel monotherapy after 6 months);
  21. Any comorbidity with estimated survival time <12 months (e.g. progressive cancer, chronic obstructive lung disease, etc.);
  22. Any contraindication to MRI examination, including implantation of an MRI-incompatible pacemaker, defibrillator, or other ferromagnetic material; etc.
  23. Pregnant or plan to be pregnant within 1 year;
  24. Any condition that may interfere with any study procedures, such as dementia, immobility, alcohol use, etc.;
  25. Planned surgery within 1 year;
  26. Taking iron supplement;
  27. Participating in any other clinical trial of an investigational drug or device that has not met its primary endpoint.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Xiaozeng Wang, MD +86-13309885930 wxiaozeng@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03198741
Other Study ID Numbers  ICMJE SYNH-20170602
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Han Yaling, Shenyang Northern Hospital
Study Sponsor  ICMJE Shenyang Northern Hospital
Collaborators  ICMJE
  • Changhai Hospital
  • ANKON medical technologies (Shanghai)Co.,LTD
Investigators  ICMJE
Principal Investigator: Yaling Han, PhD General Hospital of Shenyang Military Region
PRS Account Shenyang Northern Hospital
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP