Clinical trial NCT04810364: HIV Infection And Evolvement of Atherosclerotic Plaque
Official title: Systemic Inflammation and Progression of Atherosclerosis in HIV Patients Underwent Noninvasive and Invasive Multimodality Imaging
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Coronary Artery Disease
Atherosclerosis, Coronary
Hiv
HIV Infections
Stable Chronic Angina
Keywords: Coronary Angiography
Echocardiography
Markers of Inflammation
Lipid Profile
Percutaneous transluminal coronary angioplasty
Percutaneous coronary intervention
Coronary Artery Diseases
Atherosclerosis
HIV
Plaque burden
SYNTAX score
Fractional flow reserve
Optical coherence tomography
Intravascular ultrasound
Intravascular imaging
Lead sponsor: Central Clinical Hospital of the Russian Academy of Sciences
Sponsor class: OTHER_GOV
Collaborators: name: Moscow Regional Centre For HIV Care and Prevention
First posted: 2021-03-23
Enrollment: 1000
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All stable chest pain comers with a chronic coronary syndrome without acute angina who underwent QCA, applicable intravascular imaging (OCT, IVUS, VH-IVUS, NIRS) with or without further PCI.

Brief summary: In a prospective multi-center observational study, 200 HIV-infected patients treated with antiretroviral treatment (ART) and who suffered from coronary artery disease (CAD) will be enrolled. Blood samples for biological parameters will be collected with all participants: lipid profile and markers of systemic inflammation specific for HIV-infection (lipopolysaccharide-binding protein; cytokines: IL-1β, IL-6, IL-8, IL-10, TNF -α, INF-γ, INF-α; procalcitonin; inflammatory hsCRP).

All of them will undergo functional testing (Echo, CMR both at rest and stress if necessary) and invasive imaging with QCA, FFR, QFR, OCT, IVUS, VH-IVUS, NIRS.

Patients will be treated according to the current and previous recommendations. Both medical treatment and percutaneous transluminal coronary angioplasty (PTCA) with or without stenting will be done.

Collected data will be analyzed: correlation between ART, blood test results, coronary angiography results, including performed PTCA, history of myocardial infarctions, and other cardiovascular events.

The follow-up period will achieve 12 months prospectively with collected clinical events and imaging outcomes which will be determined at the baseline and 12-month follow-up.

The independent ethics expertise will be provided by the Central Clinical Hospital of the Russian Academy of Sciences (Moscow, Russia). The monitoring of the clinical data with imaging will be provided by The Ethics Board of Central Clinical Hospital of the Russian Academy of Sciences.

Detailed description: HIV, the virus that causes AIDS (acquired immunodeficiency syndrome), is one of the world's most serious health and development challenges. Approximately 38 million people live with HIV, and tens of millions of people have died of AIDS-related causes since the beginning of the epidemic.

However, with increasing access to effective HIV prevention, diagnosis, treatment, and care, including opportunistic infections, HIV infection has transformed from an irreversible terminal illness to chronic disease. Unfortunately, increased life expectancy has increased the risk of other chronic diseases such as cardiovascular diseases (CVD). Actually, CVD has become the most common cause of death in HIV-infected individuals. The risk of myocardial infarction and coronary atherosclerosis prevalence is nearly twice as high in people living with HIV than in the general population. Statins are effective primary prevention for CAD events; however, there are no specific statin use guidelines in HIV. Besides, there is not enough information about systemic inflammation markers and their correlation with atherosclerosis severity.

Nowadays, using invasive imaging, including quantitative coronary angiography with or without further percutaneous coronary intervention, optical coherence tomography/ OCT, intravascular ultrasound/ IVUS, VH-IVUS, near-infrared spectroscopy/ NIRS, cardiovascular events can be predicted and prevented.

In a prospective multicenter observational study, 200 HIV-infected patients treated with antiretroviral treatment (ART) and who suffered from coronary artery disease (CAD) will be enrolled. Blood samples for biological parameters will be collected with all participants: lipid profile and markers of systemic inflammation specific for HIV-infection (lipopolysaccharide-binding protein; cytokines: IL-1β, IL-6, IL-8, IL-10, TNF -α, INF-γ, INF-α; procalcitonin; inflammatory hsCRP).

All of them will undergo functional testing (Echo, CMR both at rest and stress if necessary) and invasive imaging with QCA (Quantitative Coronary Angiography), FFR (Fractional Flow Reserve), QFR (Quantitative Flow Reserve), OCT (Optical Coherence Tomography), IVUS (Intravascular Ultrasound), VH-IVUS (Virtual Histology - IVUS), NIRS (Near Infrared Spectroscopy).

Patients will be treated according to the current and previous recommendations: The 2019 HIV Russian National Guidelines; EACS Guidelines 2020; The AHA scientific statement Characteristics, Prevention, and Management of Cardiovascular Disease in People Living With HIV A Scientific Statement From the American Heart Association. Circulation 2019; ESC/EACTS Guidelines on Myocardial Revascularization 2018; 2019 Guidelines on Chronic Coronary Syndromes.

Both medical treatment and percutaneous transluminal coronary angioplasty (PTCA) with or without stenting will be provided.

The follow-up period will achieve 12 months prospectively with collected clinical events and imaging outcomes which will be determined at the baseline and 12-month follow-up.

The independent ethics expertise will be provided by the Central Clinical Hospital of the Russian Academy of Sciences (Moscow, Russia). The monitoring of the clinical data with imaging will be provided by The Ethics Board of Central Clinical Hospital of the Russian Academy of Sciences.

The clinical data of the HIVE trial include information of the complex examination with:

1. invasive imaging with QCA, FFR, QFR, OCT, IVUS, VH-IVUS, NIRS,
2. two interviews with the risk factor modification recommendations,
3. blood tests:

   * lipid profile (total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, VLDL cholesterol),
   * markers of systemic inflammation specific for HIV-infection (lipopolysaccharide-binding protein; cytokines: IL-1β, IL-6, IL-8, IL-10, TNF -α, INF-γ, INF-α; procalcitonin; inflammatory hsCRP),
   * biochemical blood test (glucose, asparagine transaminase, alanine transaminase, total bilirubin, creatinine, markers of the myocardium damage (myoglobin, troponin I, creatine kinase, creatine kinase-MB, brain natriuretic peptide - NT-proBNP),
   * complete blood count,
4. ECG,
5. Echo,
6. CMR results

The prospective patients will be tested with HeartAge, SCORE, Duke ACC/ AHA, Duke - DCS, Diamond-Forrester - DFM, The Seattle Angina Questionnaire - SAQ, DukeActivity Status Index -DASI, and EQ-5D-5L, scores that are specific for HIV: EuroSida AIDS/Death risk score, FENCE score, CSRFENCE Score. Patients will be screened for the major risk factors and their modification: unhealthy blood cholesterol levels, high blood pressure, smoking, insulin resistance, diabetes, overweight or obesity, lack of physical activity, unhealthy diet, older age, genetic or lifestyle factors, family history of early heart diseases.

The PCI and PTCA will be undergone by the 2020 ESC/EACTS Guidelines on Myocardial Revascularization. The imaging data from non-invasive (CMR, Echo) and invasive (QCA, FFR, QFR, OCT, IVUS, VH-IVUS, NIRS) methods will be handled and analyzed with the expert-level post-processing imaging software (Medis Suite Solutions: MR, XA, QFR, CT, Intravascular, Ultrasound) from Medis Medical Imaging Systems B.V. (Leiden, The Netherlands).

Our study aims to evaluate the severity of coronary atherosclerosis in HIV-patients with CAD and its correlation with markers of systemic inflammation specific for HIV-infection (LBP; cytokines: IL-1β, IL-6, IL-8, IL-10, TNF -α, INF-γ, INF-α; procalcitonin; inflammatory hsCRP) and to estimate their value in preventing cardiovascular events.

Eligibility criteria: Inclusion Criteria:

* all HIV-positive patients with chronic coronary syndrome or angina equivalent consistent with the manifestation of the stable coronary artery disease (in accordance with the 2019 Guidelines on Chronic Coronary Syndromes);
* patients who underwent CCTA (index procedure) with or without further PCI;
* age above 21 years old;
* patients must receive antiretroviral medications (in accordance to the 2019 HIV Russian National Guidelines; EACS Guidelines 2020);
* lesions may be either de novo or restenotic;
* patient must have one or two-vessel disease in a native coronary vessel requiring or not requiring PCI without indications for immediate bypass surgery with any SYNTAX score;
* successful uncomplicated PCI could be performed in the culprit vessels and all culprit lesions, but there should be no events or complications between the procedures of PCI in the past and 6 months prior to admission to the Chest Pain Center
* the non-culprit vessel should have no flow-limiting lesions (diameter stenosis \<39%, but any plaque burden) and must be available for imaging.The non-culprit vessel must be considered safe for imaging evaluation;

Exclusion Criteria:

* any acute comorbidities;
* patient has had a documented ST-elevation acute myocardial infarction within the 24 hours prior to admission to the Chest Pain Center;
* unprotected left main lesion location;
* culprit lesion is located within or distal to an arterial or saphenous vein graft;
* untreated significant coronary lesion with a \>50-75% diameter stenosis remaining in the culprit vessel after the planned intervention (branch stenosis is permitted);
* lesion or vessel contains visible thrombus within the imaging procedure;
* patient has an additional lesion that requires intervention within 180 days after the initial hospitalization;
* any diameter stenosis more than 75% in the non-culprit vessel;
* indications for immediate bypass surgery within one year of enrollment with the SYNTAX above 34 (multi-vessel disease requiring intervention in all three major coronary arteries);
* creatinine \>150 mmol/L;
* need for dialysis;
* severe endocrine disorders (diabetes is permitted) including pre-existing thyroid diseases;
* decompensated hypotension or heart failure requiring intubation, inotropes,intravenous diuretics, or intra-aortic balloon counterpulsation;
* patient has a known hypersensitivity, allergy, or contraindication to any of the following: aspirin, heparin, clopidogrel, and ticlopidine, or to contrast that cannot be adequately pre-medicated;
* presence of cardiac implants;
* presence of cardiogenic shock;
* patient has a known left ventricular ejection fraction \<39%;
* refractory ventricular arrhythmia;
* acute conduction system disease requiring a pacemaker;
* patient has had a recent PCI (last 6 months prior to admission to the Chest Pain Center) unless the patient is undergoing a staged procedure for dual vessel treatment
* prior participation in this study or patient is currently enrolled in another investigational use device, imaging, or drug study that has not been reached its primary endpoint;
* mental diseases, inability for cooperation;
* pregnancy;
* stroke or CVA;
* gastrointestinal bleeding.

Primary outcomes:
measure: Change of per cent of plaque burden from baseline to follow-up as assessed by QCA
timeFrame: At 12 months after the baseline imaging procedure
measure: Number of participants with major adverse cardiac events that are related to plaque burden
timeFrame: At 12 months after the baseline imaging procedure
measure: Diagnostic value of systemic inflammation markers for risk stratification
timeFrame: At 12 months after the blood testing and the baseline imaging procedure
measure: Invasive assessment of fractional flow reserve for risk stratification
timeFrame: At 12 months after the baseline imaging procedure
Secondary outcomes:
measure: Change of serologic marker of inflammation CRP from baseline to follow-up
timeFrame: At 12 months after the baseline imaging procedure
measure: Number of participants with procedural success
timeFrame: At 12 months after the baseline imaging procedure
measure: Change of complexity of coronary artery disease from baseline to follow-up as assessed by SYNTAX score I
timeFrame: At 12 months after the baseline imaging procedure
measure: Change of complexity of coronary artery disease from baseline to follow-up as assessed by SYNTAX score II
timeFrame: At 12 months after the baseline imaging procedure
measure: Change of fractional flow reserve (FFR) from baseline to follow-up that are related to the progress of atherosclerosis
timeFrame: At 12 months after the baseline imaging procedure
measure: Change of complexity of coronary artery disease from baseline to follow-up as assessed by Leaman Coronary Score
timeFrame: At 12 months after the baseline imaging procedure
measure: Number of participants with encephalopathy
timeFrame: At 12 months after the baseline imaging procedure
measure: Number of chest pain patients with non-obstructive coronary artery disease
timeFrame: At 12 months after the baseline imaging procedure
measure: Number of chest pain patients without coronary artery disease
timeFrame: At 12 months after the baseline imaging procedure
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital of the Russian Academy of Sciences
city: Moscow
country: Russian Federation
facility: Moscow Regional Centre For HIV Care and Prevention
Study officials:
affiliation: Central Clinical Hospital of the Russian Academy of Sciences
name: Diana Izimarieva, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Moscow Regional Centre For HIV Care and Prevention
name: Elena Orlova-Morozova, MD, PhD
role: STUDY_DIRECTOR
affiliation: Central Clinical Hospital of the Russian Academy of Sciences
name: Alexey Sozykin, MD, D.Sc
role: STUDY_CHAIR
affiliation: Central Clinical Hospital of the Russian Academy of Sciences
name: Alexey Nikitin, M.D., D.Sc., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Central Clinical Hospital of the Russian Academy of Sciences
name: Eugene Averin, M.D., D.Sc., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Pirogov Russian National Research Medical University
name: Alexey Shevchenko, M.D., D.Sc., Ph.D.
role: STUDY_DIRECTOR
References: