Comparison of Anticoagulation Prolongation vs. no Anticoagulation in STEMI Patients After Primary PCI (RIGHT)

• ClinicalTrials.gov Identifier: NCT03664180
• Recruitment Status: Completed
• First Posted: September 10, 2018
• Last Update Posted: May 3, 2023
• Sponsor: Beijing Anzhen Hospital
• Collaborators: Chinese Academy of Medical Sciences, Fuwai Hospital; ACTION Study Group (Pitié-Salpêtrière Hospital), Paris, France
• Information provided by (Responsible Party): Shao-Ping Nie, Beijing Anzhen Hospital

Tracking Information

• First Submitted Date: August 27, 2018
• First Posted Date: September 10, 2018
• Last Update Posted Date: May 3, 2023
• Actual Study Start Date: January 11, 2019
• Actual Primary Completion Date: November 23, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 7, 2018)

• Primary efficacy endpoint - number of event of a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, stent thrombosis (definite) or urgent revascularization (any vessel) [ Time Frame: 30 days ]
  The number of event of a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, stent thrombosis (definite) or urgent revascularization (any vessel) within 30 days after randomization
• Primary safety endpoint - The number of event of major bleeding [ Time Frame: 30 days ]
  The number of event of major bleeding (BARC 3 to 5) within 30 days after randomization

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 7, 2018)

• Secondary ischemic endpoints - The number of event of a composite of all-cause death, non-fatal myocardial infarction, or non-fatal stroke [ Time Frame: 30 days ]
  The number of event of a composite of all-cause death, non-fatal myocardial infarction, or non-fatal stroke within 30 days after randomization
• Secondary ischemic endpoints - The number of event of a composite of all-cause death or non-fatal myocardial infarction [ Time Frame: 30 days ]
  The number of event of a composite of all-cause death or non-fatal myocardial infarction within 30 days after randomization
• Secondary ischemic endpoints - The number of cardiovascular death events [ Time Frame: 30 days ]
  The number of cardiovascular death event within 30 days after randomization
• Secondary ischemic endpoints - The number of stent thrombosis (ARC definite) events [ Time Frame: 30 days ]
  The number of stent thrombosis (ARC definite) event within 30 days after randomization
• Secondary safety endpoints - The number of bleeding events (TIMI, STEEPLE and GUSTO definition) [ Time Frame: 30 days ]
  The number of bleeding events (TIMI, STEEPLE and GUSTO definition) within 30 days after randomization To demonstrate that post-procedure anticoagulation with UFH, enoxaparin or bivalirudin as compared to their placebo is associated to lower rate of the composite endpoint of major bleeding according to TIMI, STEEPLE and GUSTO definitions within the first 30 days after randomization.
• Secondary safety endpoints - The number of thrombocytopenia events [ Time Frame: 30 days ]
  The number of thrombocytopenia events within 30 days after randomization To demonstrate superiority of a strategy of post-procedure anticoagulation with UFH, enoxaparin or bivalirudin as compared to their placebo by the time from randomization to the first occurrence of any event of the Thrombocytopenia endpoint over 30 days of follow-up.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparison of Anticoagulation Prolongation vs. no Anticoagulation in STEMI Patients After Primary PCI
• Official Title: Randomized Comparison of Anticoagulation After Primary Percutaneous Coronary Intervention Using Enoxaparin, ACT Guided Unfractionated Heparin or Bivalirudin Prolongation vs. no Anticoagulation To Improve Clinical Outcome
• Brief Summary: The RIGHT study is a large randomized study dedicated to post-PPCI anticoagulation in STEMI patients. The investigators propose to evaluate the clinical efficacy and safety of anticoagulation prolonged for at least 48 hours after the procedure vs. no prolongation of anticoagulation after procedure in patients with STEMI treated with bivalirudin during PPCI (primary hypothesis). When allocated to anticoagulation prolongation by randomization, the subject will be assigned to UFH, enoxaparin or bivalirudin (same regimen allocated by centre) for at least 48 hours after PPCI. The results from this study are expected to provide guidance on the risk/benefit of post-procedural anticoagulation in patients with STEMI.
• Detailed Description: A minor change of time of randomization after prolongation of bivalirudin infusion at PCI dose up to 4 hours on protocol at September 19,2018. Reasons: a minor change concerning the timing of randomization considering the current local practice in some centers that use the 4 hour infusion of bivalirudin just after PCI. It remains in agreement with the current international guidelines and with the drug label in China. There is no change in drugs used and doses of these drugs once the randomization occurs.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: STEMI - ST Elevation Myocardial Infarction

Intervention

• Drug: Bivalirudin
  IV infusion of 0.2 mg/kg/h (low-rate infusion) for at least 48h after the procedure or until discharge from CCU if it occurs later
• Drug: Enoxaparin
  40mg/d s.c.for at least 48h after the procedure or until discharge from CCU if it occurs later
• Drug: Unfractionated heparin
  IV infusion of 10 U/kg/h (maximum 1000 U) initially, adjusted to maintain ACT between 150 and 220 seconds for at least 48h after the procedure or until discharge from CCU if it occurs later
• Drug: Bivalirudin placebo
  Matching placebo IV infusion for at least 48h after the procedure or until discharge from CCU if it occurs later
• Drug: Enoxaparin placebo syringe
  Placebo syringe will be only prepared by a designated unblended medical professional on site. Placebo syringe will be presented in identical containers as a clear, colorless, sterile liquid of saline.Subcutaneous injection once a day for at least 48 hours after the procedure or until discharge from CCU if it occurs later.
• Drug: Unfractionated heparin placebo
  Matching placebo IV infusion for at least 48h after the procedure or until discharge from CCU if it occurs later.

Study Arms

• Experimental: anticoagulation
  Interventions:

  • Drug: Bivalirudin
  • Drug: Enoxaparin
  • Drug: Unfractionated heparin
• Placebo Comparator: No anticoagulation
  Interventions:

  • Drug: Bivalirudin placebo
  • Drug: Enoxaparin placebo syringe
  • Drug: Unfractionated heparin placebo

• Publications *: Yan Y, Wang X, Guo J, Li Y, Ai H, Gong W, Que B, Zhen L, Lu J, Ma C, Montalescot G, Nie S. Rationale and design of the RIGHT trial: A multicenter, randomized, double-blind, placebo-controlled trial of anticoagulation prolongation versus no anticoagulation after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Am Heart J. 2020 Sep;227:19-30. doi: 10.1016/j.ahj.2020.06.005. Epub 2020 Jun 20.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 30, 2023): 2989
• Original Estimated Enrollment (submitted: September 7, 2018): 2856
• Actual Study Completion Date: November 23, 2022
• Actual Primary Completion Date: November 23, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age ≥18 years old
• STEMI with PPCI of culprit lesion
• Bivalirudin therapy during PPCI
• Signed informed consent form

Exclusion Criteria:

• Patients with a formal indication for anticoagulation after PPCI (e.g. atrial fibrillation, left-ventricular thrombus, intra-aortic balloon pump, pulmonary embolism, mechanical heart valve)
• Patients with any indication for chronic anticoagulation
• Patient with previous lytic treatment
• Patient with previous coronary artery bypass graft surgery
• Cardiogenic shock, malignant ventricular arrhythmia, or mechanical complications
• Any anticoagulation other than bivalirudin started after the procedure before randomization
• Estimated body weight of >120 kg or <45kg
• BP ≥180/110mmHg at randomization
• Any bleeding diathesis or severe hematologic disease or history of intracerebral mass, aneurysm, arteriovenous malformation, recent (<6months) ischemic stroke or TIA, recent (<6months) intracranial hemorrhage or, gastrointestinal or genitourinary bleeding within the past 2 weeks
• History of heparin-induced thrombocytopenia
• Suspected acute aortic dissection (AAD)
• Major surgery within 1 month
• A planned elective surgical procedure that would necessitate an interruption in treatment with P2Y12 inhibitors in the next 6 months after enrollment
• Known PLT≤100×109 or HGB≤10g/L
• Known transaminase >3-fold ULN, or CCr<30ml/min
• Known allergy to any study drug
• Pregnancy or lactation
• Noncardiac coexisting conditions that could limit life expectancy to less than 1 year
• Current participation in an investigational drug or device trial

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03664180
• Other Study ID Numbers: 2018024X; BJUHFRIGHT201802 ( Other Identifier: Beijing United Heart Foundation )
• 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
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Shao-Ping Nie, Beijing Anzhen Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Beijing Anzhen Hospital
• Original Study Sponsor: Same as current

Collaborators

• Chinese Academy of Medical Sciences, Fuwai Hospital
• ACTION Study Group (Pitié-Salpêtrière Hospital), Paris, France

• Investigators: Not Provided
• PRS Account: Beijing Anzhen Hospital
• Verification Date: April 2023