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Comparison of the Incidence of Major Cardiovascular Events Between the Combination of Percutaneous Intervention and Optimal Drug Therapy and the Optimal Drug Therapy Alone in Patients With Chronic Coronary Syndrome (PIVOT)

15. Mai 2026 aktualisiert von: Jung-Kyu Han, Seoul National University Hospital

Percutaneous Intervention Versus Optimal Medical Therapy in Chronic Coronary Syndrome (PIVOT) Trial

Comparison of the incidence of major cardiovascular events between the combination of percutaneous intervention and optimal drug therapy and the optimal drug therapy alone in patients with chronic coronary syndrome.

  • Main RCT (Randomized Clinical Trial): Patients with chronic coronary syndrome enrolled in the study will be randomized in a 1:1 ratio to either 1) PCI(Percutaneous Coronary Intervention) plus optimal medical therapy or 2) optimal medical therapy alone, with clinical outcomes assessed during follow-up. (2,301 participants)
  • Nested RCT: An embedded randomized supplementary study was conducted on a subset (220 participants) of the total subjects.

In patients who have decided to use beta-blockers for the control of angina, additional 1:1 randomization evaluates the efficacy of carvedilol sustained-release (SR) and immediate-release (IR) formulations. Both formulations are targeted for use up to the maximal tolerated dose, taking into account patient symptoms.

Studienübersicht

Status

Noch keine Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

Background:

In patients with chronic coronary syndrome (CCS), the role of percutaneous coronary intervention (PCI) beyond symptom relief - particularly in preventing future major cardiovascular events - remains an area of active debate. Landmark trials such as COURAGE and ISCHEMIA raised questions about the incremental benefit of PCI over optimal medical therapy (OMT) alone; however, both trials allowed crossover from the medical arm to PCI, and included periprocedural myocardial infarction (MI) in their primary endpoints, which may have diluted the observed treatment effects. Moreover, since those trials were conducted, both PCI techniques and pharmacological therapies have advanced substantially. Imaging-guided PCI using intravascular ultrasound (IVUS) or optical coherence tomography (OCT) has been shown to reduce adverse cardiac events, and lipid-lowering strategies have been further strengthened by the addition of ezetimibe and PCSK9 inhibitors. Against this background, a rigorous re-evaluation of PCI's role in CCS, using contemporary devices and a more conservative definition of clinically driven revascularization, is warranted.

Study Design:

The PIVOT trial is a multicenter, prospective, open-label, randomized controlled trial conducted at multiple sites in South Korea. Eligible patients with CCS who have a functionally or anatomically significant coronary stenosis confirmed by coronary angiography are randomized 1:1 to either (1) PCI plus optimal medical therapy or (2) optimal medical therapy alone. Randomization is stratified by participating center and sex using a web-based system managed independently by the Medical Research Collaborating Center (MRCC).

Main RCT - Intervention:

In the PCI arm, the target lesion(s) are treated with drug-eluting stent(s) according to each site's standard practice. Imaging-guided PCI with IVUS or OCT is strongly recommended and is mandatory for complex PCI cases. The BioFreedom ULTRA stent (polymer-free, Biolimus A9-coated) is used preferentially; other approved drug-eluting stents may be used when clinically indicated. Following PCI, dual antiplatelet therapy is maintained for 6 months per guideline recommendation, with adjustments permissible based on individual bleeding and ischemic risk. Both arms receive guideline-directed optimal medical therapy, including intensive lipid-lowering treatment (LDL-C target <55 mg/dL), antiplatelet agents, and anti-anginal medications as indicated. Lifestyle interventions (smoking cessation, weight management, dietary modification, and physical activity) are also recommended.

Primary Endpoint (Main RCT):

Patient-oriented composite outcome (POCO): a composite of cardiovascular death, non-fatal myocardial infarction, or clinically driven revascularization at 2 years after completion of enrollment. Periprocedural MI is excluded from the primary endpoint. The trial is powered for superiority (one-sided α = 0.025, power = 90%), assuming a 2-year POCO rate of 12.0% in the OMT arm and 8.5% in the PCI arm. A total of 2,301 participants are required.

Follow-up:

Participants are followed at 6 months, 1, 2, 3, 4, and 5 years after enrollment (±90 days). Clinical outcomes, vital signs, laboratory tests, concomitant medications, and angina-related quality of life (Seattle Angina Questionnaire-7, SAQ-7) are assessed at every visit. Long-term follow-up up to 5 years after the last enrolled patient is planned to evaluate durability of treatment effects.

Nested RCT - Design and Rationale:

An embedded, independently randomized substudy (Nested RCT) is conducted within the PIVOT trial. Among participants in the main trial for whom beta-blocker therapy is deemed clinically appropriate - based on pre-specified criteria including heart rate control needs, history of prior MI, concurrent hypertension, tachyarrhythmia, or intolerance to calcium channel blockers - an additional 1:1 randomization is performed to compare carvedilol sustained-release (SR) versus immediate-release (IR) formulations. This substudy addresses the evidence gap regarding whether the two formulations are clinically equivalent in terms of angina symptom control in CCS patients, as head-to-head randomized data are currently lacking despite both being widely prescribed.

Nested RCT - Intervention:

Participants assigned to the SR arm receive carvedilol SR (Dilatrend SR; starting dose 32 mg once daily, up-titrated to 64 mg or 128 mg as tolerated). Participants assigned to the IR arm receive carvedilol IR (Dilatrend; starting dose 12.5 mg twice daily, up-titrated to 25 mg twice daily or 50 mg twice daily as tolerated). Both formulations are titrated to the maximal tolerated dose with a resting heart rate target of 55-60 bpm. Medication adherence is assessed by pill count at 6 and 12 months.

Primary Endpoint (Nested RCT):

Change in SAQ-7 Summary score from baseline to 12 months. Non-inferiority of carvedilol SR versus IR is concluded if the lower bound of the 95% confidence interval for the between-group difference exceeds -5 points, analyzed by ANCOVA adjusting for baseline SAQ-7 score. A total of 220 participants are required (one-sided α = 0.025, power = 80%, non-inferiority margin Δ = 5 points).

Statistical Analysis:

For the main RCT, the primary endpoint is analyzed using the Kaplan-Meier method with a stratified log-rank test in the intention-to-treat (ITT) population. Secondary time-to-event endpoints are analyzed using the cumulative incidence function with a Fine and Gray model, treating death as a competing risk. The Nested RCT primary endpoint is analyzed by ANCOVA in both the ITT and per-protocol (PP) populations.

Studientyp

Interventionell

Einschreibung (Geschätzt)

2301

Phase

  • Unzutreffend

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studienorte

  • Südkorea
      • Busan, Südkorea, 49241
        • Pusan National University Hospital
        • Kontakt:
      • Busan, Südkorea, 48108
        • Inje University Haeundae Paik Hospital
        • Kontakt:
      • Busan, Südkorea, 49267
        • Kosin University Gospel Hospital
        • Kontakt:
      • Daegu, Südkorea, 41944
        • Kyungpook National University Hospital
        • Kontakt:
      • Daegu, Südkorea, 41931
        • Keimyung University Dongsan Hospital
        • Kontakt:
      • Daejeon, Südkorea, 35015
        • Chungnam National University Hospital
        • Kontakt:
      • Daejeon, Südkorea, 34943
        • The Catholic University of Korea Daejeon St. Mary's Hospital
        • Kontakt:
      • Gwangju, Südkorea, 61469
        • Chungnam National University Hospital
        • Kontakt:
      • Jeju City, Südkorea, 63241
        • Jeju National University Hospital
        • Kontakt:
      • Seoul, Südkorea, 08308
        • Koera University Guro Hospital
        • Kontakt:
      • Seoul, Südkorea, 07061
        • Seoul Metropolitan Government Seoul National University Boramae Medical Center
        • Kontakt:
      • Seoul, Südkorea, 07804
        • Ewha Womans University Medical Center
        • Kontakt:
      • Seoul, Südkorea, 05355
        • Kangdong Sacred Heart Hospital
        • Kontakt:
      • Ulsan, Südkorea, 44033
        • Ulsan Univeristy Hospital
        • Kontakt:
    • Gangwon-do
      • Chuncheon, Gangwon-do, Südkorea, 24289
        • Kangwon National University Hospital
        • Kontakt:
      • Gangneung, Gangwon-do, Südkorea, 25440
        • GangNeung Asan Hospital
        • Kontakt:
    • Gyeonggi-do
      • Anyang-si, Gyeonggi-do, Südkorea, 14068
        • Hallym University Medical Center
        • Kontakt:
      • Bucheon-si, Gyeonggi-do, Südkorea, 14754
        • Bucheon Sejong Hospital
        • Kontakt:
      • Goyang-si, Gyeonggi-do, Südkorea, 10380
        • Inje University Ilsan Paik Hospital
        • Kontakt:
    • Gyeongsangnam-do
      • Changwon, Gyeongsangnam-do, Südkorea, 51353
        • Samsung Changwon Medical Center
        • Kontakt:

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

  • Erwachsene
  • Älterer Erwachsener

Akzeptiert gesunde Freiwillige

Nein

Beschreibung

Inclusion Criteria:

  • Patients aged 40 years or older
  • Patients suspected of having chronic coronary syndrome who have undergone coronary angiography and confirmed stenotic lesions

  • Patients with lesions suitable for stent insertion who have 50% or more visually estimated stenosis in major coronary arteries with a diameter of 2.5 mm or greater observed on coronary angiography, and who satisfy one or more of the following conditions:

    1. Patients with stenosis of 70% or more confirmed via Quantitative coronary angiography (50% or more for the left main coronary artery)
    2. Minimum lumen area (MLA) ≤ 4 mm² or plaque burden >70% on intravascular ultrasound (IVUS)
    3. MLA <3.5 mm² or area stenosis (AS) >65% on Optical Coherence Tomography (OCT)
    4. The corresponding stenosis on localizing stress imaging using SPECT or PET When there is a significant focal ischemic deficit in the coronary artery region of the lesion and the total perfusion deficit (TPD) is ≥10%
    5. Pressure wire-based fractional flow reserve (FFR) ≤0.80
  • Patients who can verbally confirm their understanding of invasive physiological or imaging evaluations and the benefits, harms, and alternative treatments of coronary angioplasty using drug-eluting stents, and for whom the patient or their legal representative can submit a written consent form.

Additional Criteria for nested RCT Studies

  • When heart rate control is deemed therapeutically important due to an accompanying increase in heart rate at rest or during symptomatic episodes.
  • When the use of beta-blockers is deemed clinically advantageous due to a history of myocardial infarction.
  • When beta-blockers can help control blood pressure and symptoms in cases of concomitant hypertension.
  • When there is a clinical situation requiring associated tachyarrhythmia or heart rate control.
  • When beta-blockers are deemed more appropriate due to a history of contraindications, intolerance, or side effects of calcium channel blockers.

Exclusion Criteria:

  • Patients with Left Ventricular Ejection Fraction (LVEF) less than 35%
  • Patients with cardiogenic shock
  • Patients with pulmonary edema or heart failure unresponsive to standard treatment
  • Patients with unstable angina whose symptoms persist despite maximal drug therapy
  • Patients with a history of ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), or unstable angina within the last 6 months
  • Patients with active bleeding
  • Patients with major bleeding of the gastrointestinal or urinary system within the last 3 months
  • Patients with coagulation disorders prone to bleeding (including heparin-induced thrombocytopenia)
  • Patients with hypersensitivity to or contraindications to the following drugs: Heparin, Aspirin, Clopidogrel, Prasugrel, Contrast media (Patients sensitive to contrast media are not excluded if the condition can be effectively prevented through pretreatment with steroids or diphenhydramine (e.g., flare-ups).
  • Patients for whom percutaneous coronary intervention (PCI) is contraindicated
  • Patients who have already undergone coronary artery bypass grafting (CABG)
  • Patients with in-stent restenosis in the target lesion
  • Patients with chronic total occlusion (CTO) in major coronary arteries
  • Patients with lesions having an FFR of less than 0.64
  • Patients with coronary arteries that are anatomically unsuitable for both PCI and CABG
  • Patients with non-ischemic dilated cardiomyopathy or hypertrophic cardiomyopathy
  • Patients with severe valvular disease or those judged by the investigator to be likely to require valve surgery or percutaneous valve replacement during the study period
  • Patients with non-cardiac diseases, etc., with a life expectancy of less than one year or expected to have low treatment adherence (at the investigator's judgment)
  • Pregnant or breastfeeding patients
  • Other patients deemed by the investigator to be unsuitable for participation in the clinical trial

Additional Criteria for nested RCT Studies

  • Significant bradycardia at rest, second-degree or higher atrioventricular block, or significant conduction disturbance
  • Bronchial asthma or clinically significant bronchospasmodic disease
  • Symptomatic hypotension
  • Variant angina as a main presentation
  • Other cases where the supervising investigator deems the use of beta-blockers medically inappropriate

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: PCI
PCI will be performed in addition to guideline-directed optimal medical therapy
Verfahren: percutaneous coronary intervention
PCI will be performed in addition to optimal medical therapy.
Arzneimittel: Guideline-directed Optimal Medical treatment
Guideline-directed optimal medical therapy alone without PCI
Arzneimittel: Carvedilol Sustained-Release (SR) (Nested RCT subset)
Carvedilol SR (Dilatrend SR; 8/16/32/64 mg) once daily, starting at 32 mg and up-titrated to maximal tolerated dose (up to 128 mg). Applied to Nested RCT participants only (n=220 total across both arms), in whom eligible participants are independently randomized 1:1 to either carvedilol SR or IR - only one formulation is assigned per participant.
Arzneimittel: Carvedilol Immediate-Release (IR) (Nested RCT subset)
Carvedilol IR (Dilatrend; 3.125/6.25/12.5/25 mg) twice daily, starting at 12.5 mg BID and up-titrated to maximal tolerated dose (up to 50 mg BID). Applied to Nested RCT participants only (n=220 total across both arms), in whom eligible participants are independently randomized 1:1 to either carvedilol SR or IR - only one formulation is assigned per participant.
Aktiver Komparator: Guideline-directed Optimal Medical treatment
Optimal medical therapy alone without PCI
Arzneimittel: Guideline-directed Optimal Medical treatment
Guideline-directed optimal medical therapy alone without PCI
Arzneimittel: Carvedilol Sustained-Release (SR) (Nested RCT subset)
Carvedilol SR (Dilatrend SR; 8/16/32/64 mg) once daily, starting at 32 mg and up-titrated to maximal tolerated dose (up to 128 mg). Applied to Nested RCT participants only (n=220 total across both arms), in whom eligible participants are independently randomized 1:1 to either carvedilol SR or IR - only one formulation is assigned per participant.
Arzneimittel: Carvedilol Immediate-Release (IR) (Nested RCT subset)
Carvedilol IR (Dilatrend; 3.125/6.25/12.5/25 mg) twice daily, starting at 12.5 mg BID and up-titrated to maximal tolerated dose (up to 50 mg BID). Applied to Nested RCT participants only (n=220 total across both arms), in whom eligible participants are independently randomized 1:1 to either carvedilol SR or IR - only one formulation is assigned per participant.

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Change in Seattle Angina Questionnaire-7 (SAQ-7) Summary Score from Baseline to 12 Months (for Nested RCT)
Zeitfenster: One year after registration
This outcome applies to the Nested RCT substudy only (n=220), in which participants eligible for beta-blocker therapy are independently randomized 1:1 to carvedilol SR or IR, regardless of their main trial allocation. The SAQ-7 is a 7-item validated questionnaire assessing angina-related health status across three domains: physical limitation, angina frequency, and quality of life. Scores range from 0 to 100, with higher scores indicating fewer symptoms and better quality of life. The SAQ-7 Summary score is calculated as the mean of the three domain scores.
One year after registration
Number of Participants with Patient-oriented composite outcome (POCO), defined as the composite of cardiovascular death, non-fatal myocardial infarction (MI), or clinically driven revascularization
Zeitfenster: 2nd year and 5th year since registration was complete

This outcome applies to the main RCT (n=2,301). POCO is a composite of three components: (1) cardiovascular death; (2) non-fatal myocardial infarction, excluding periprocedural MI; and (3) clinically driven revascularization. The first occurrence of any component is counted as the primary event per participant.

Clinically driven revascularization is defined as revascularization of a coronary segment with diameter stenosis ≥50% by quantitative coronary angiography, accompanied by at least one of the following: ischemic ECG(Electrocardiogram) changes at rest; typical ischemic symptoms refractory to medical therapy; unstable angina; positive invasive physiologic test (FFR(Fractional Flow Reserve) ≤0.80 or iFR (Instantaneous Wave-Free Ratio) ≤0.89); or angiographic progression with diameter stenosis ≥70% by quantitative coronary angiography regardless of other criteria.
2nd year and 5th year since registration was complete

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Number of Participants with All-cause death
Zeitfenster: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Cardiovascular death
Zeitfenster: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Cardiovascular Death or Non-Fatal Myocardial Infarction
Zeitfenster: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Myocardial Infarction
Zeitfenster: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Spontaneous myocardial infarction
Zeitfenster: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Periprocedural myocardial infarction
Zeitfenster: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Periprocedural myocardial infarction, as defined by the Fourth Universal Definition of Myocardial Infarction
Zeitfenster: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Ischemic stroke
Zeitfenster: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Stent thrombosis
Zeitfenster: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Transient ischemic attack
Zeitfenster: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Clinically driven revascularization
Zeitfenster: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with any revascularization
Zeitfenster: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with ischemia driven revascularization
Zeitfenster: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Major bleeding events
Zeitfenster: 2nd year and 5th year since registration was complete
BARC(Bleeding Academic Research Consortium) classification, type 3 or 5
2nd year and 5th year since registration was complete
Number of Participants with Clinically relevant non-major bleeding events
Zeitfenster: 2nd year and 5th year since registration was complete
BARC(Bleeding Academic Research Consortium) classification, type 2
2nd year and 5th year since registration was complete

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Seoul National University Hospital

Mitarbeiter

Chong Kun Dang Pharmaceutical
Diomedical

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Geschätzt)

27. April 2026

Primärer Abschluss (Geschätzt)

27. April 2030

Studienabschluss (Geschätzt)

10. März 2034

Studienanmeldedaten

Zuerst eingereicht

4. Mai 2026

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

4. Mai 2026

Zuerst gepostet (Tatsächlich)

11. Mai 2026

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

19. Mai 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

15. Mai 2026

Zuletzt verifiziert

1. Mai 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • H-2601-092-1709

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

NEIN

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

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