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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. května 2026 aktualizováno: 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.

Přehled studie

Postavení

Zatím nenabíráme

Podmínky

Intervence / Léčba

Detailní popis

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.

Typ studie

Intervenční

Zápis (Odhadovaný)

2301

Fáze

  • Nelze použít

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní kontakt

  • Jméno: Jung-Kyu Han, MD, PhD
  • Telefonní číslo: +82-2-2072-4870
  • E-mail: hpcrates@gmail.com

Studijní místa

  • Jižní Korea
      • Busan, Jižní Korea, 49241
        • Pusan National University Hospital
        • Kontakt:
      • Busan, Jižní Korea, 48108
        • Inje University Haeundae Paik Hospital
        • Kontakt:
          • Dong-Kie Kim, MD, PhD
          • Telefonní číslo: 82-10-4595-9515
          • E-mail: imnpymd@gmail.com
      • Busan, Jižní Korea, 49267
        • Kosin University Gospel Hospital
        • Kontakt:
      • Daegu, Jižní Korea, 41944
        • Kyungpook National University Hospital
        • Kontakt:
      • Daegu, Jižní Korea, 41931
        • Keimyung University Dongsan Hospital
        • Kontakt:
      • Daejeon, Jižní Korea, 35015
        • Chungnam national university hospital
        • Kontakt:
      • Daejeon, Jižní Korea, 34943
        • The Catholic University of Korea Daejeon St. Mary's Hospital
        • Kontakt:
      • Gwangju, Jižní Korea, 61469
        • Chungnam national university hospital
        • Kontakt:
      • Jeju City, Jižní Korea, 63241
        • Jeju National University Hospital
        • Kontakt:
      • Seoul, Jižní Korea, 08308
        • Koera University Guro Hospital
        • Kontakt:
          • Dong Oh Kang, MD, PhD
          • Telefonní číslo: 821091486979
          • E-mail: gelly9@naver.com
      • Seoul, Jižní Korea, 07061
        • Seoul Metropolitan Government Seoul National University Boramae Medical Center
        • Kontakt:
      • Seoul, Jižní Korea, 07804
        • Ewha Womans University Medical Center
        • Kontakt:
      • Seoul, Jižní Korea, 05355
        • Kangdong Sacred Heart Hospital
        • Kontakt:
      • Ulsan, Jižní Korea, 44033
        • Ulsan Univeristy Hospital
        • Kontakt:
    • Gangwon-do
      • Chuncheon, Gangwon-do, Jižní Korea, 24289
        • Kangwon National University Hospital
        • Kontakt:
      • Gangneung, Gangwon-do, Jižní Korea, 25440
        • GangNeung Asan Hospital
        • Kontakt:
    • Gyeonggi-do
      • Anyang-si, Gyeonggi-do, Jižní Korea, 14068
        • Hallym University Medical Center
        • Kontakt:
      • Bucheon-si, Gyeonggi-do, Jižní Korea, 14754
        • Bucheon Sejong Hospital
        • Kontakt:
      • Goyang-si, Gyeonggi-do, Jižní Korea, 10380
        • Inje University Ilsan Paik Hospital
        • Kontakt:
    • Gyeongsangnam-do
      • Changwon, Gyeongsangnam-do, Jižní Korea, 51353
        • Samsung Changwon Medical Center
        • Kontakt:
          • Seung do Lee, MD, PhD
          • Telefonní číslo: 82-10-5058-0483
          • E-mail: lsd0483@gmail.com

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

  • Dospělý
  • Starší dospělý

Přijímá zdravé dobrovolníky

Ne

Popis

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

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: PCI
PCI will be performed in addition to guideline-directed optimal medical therapy
Postup: percutaneous coronary intervention
PCI will be performed in addition to optimal medical therapy.
Lék: Guideline-directed Optimal Medical treatment
Guideline-directed optimal medical therapy alone without PCI
Lék: 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.
Lék: 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.
Aktivní komparátor: Guideline-directed Optimal Medical treatment
Optimal medical therapy alone without PCI
Lék: Guideline-directed Optimal Medical treatment
Guideline-directed optimal medical therapy alone without PCI
Lék: 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.
Lék: 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.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Change in Seattle Angina Questionnaire-7 (SAQ-7) Summary Score from Baseline to 12 Months (for Nested RCT)
Časové okno: 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
Časové okno: 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

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Number of Participants with All-cause death
Časové okno: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Cardiovascular death
Časové okno: 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
Časové okno: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Myocardial Infarction
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Ischemic stroke
Časové okno: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with Stent thrombosis
Časové okno: 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
Časové okno: 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
Časové okno: 2nd year and 5th year since registration was complete
2nd year and 5th year since registration was complete
Number of Participants with any revascularization
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Seoul National University Hospital

Spolupracovníci

Chong Kun Dang Pharmaceutical
Diomedical

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Odhadovaný)

27. dubna 2026

Primární dokončení (Odhadovaný)

27. dubna 2030

Dokončení studie (Odhadovaný)

10. března 2034

Termíny zápisu do studia

První předloženo

4. května 2026

První předloženo, které splnilo kritéria kontroly kvality

4. května 2026

První zveřejněno (Aktuální)

11. května 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

19. května 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

15. května 2026

Naposledy ověřeno

1. května 2026

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

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Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

NE

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Studuje lékový produkt regulovaný americkým FDA

Ne

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

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