Clinical trial NCT04183465: Physical Activity Intervention in ELderly Patients with Myocardial INfarction
Official title: Effectiveness of an Early, Tailored, Physical Activity Intervention in ELderly Patients with Myocardial INfarction: the PIpELINe Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Myocardial Infarction
Aging
Lead sponsor: University Hospital of Ferrara
Sponsor class: OTHER
Collaborators: name: Azienda Usl di Bologna
name: Azienda Unita Sanitaria Locale di Piacenza
First posted: 2019-12-03
Enrollment: 512
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Elderly patients presenting with myocardial infarction (MI) are the highest risk population with the worst prognosis. No trial has ever been designed to optimize their outcome through a systematic improvement of their physical performance. Cardiac rehabilitation demonstrated to improve prognosis of patients after MI. However, real-life data shows that older patients are not referred to rehabilitation centers or they have low rate of attendance because of the high number of rehabilitation sessions and of logistic problems. So, data about effectiveness of rehabilitation programs in older MI patients is lacking.

The "Physical Activity Intervention for Elderly Patients with Reduced Physical Performance after acute coronary syndrome (HULK)" pilot study (NCT03021044) enrolled older MI patients and it demonstrated the feasibility and effectiveness of an early, tailored and low-cost physical activity intervention in terms of physical performance assessed by Short Physical Performance Battery (SPPB) score, that is strongly related to prognosis. The HULK study was focused on exercise training and not powered for hard endpoints. If a multi-domain lifestyle intervention in an adequately powered study may further improve prognosis is unknown. Thus, the investigator's hypothesis for the PIpELINe trial is that an early, tailored and low-cost multi-domain lifestyle intervention may improve prognosis of older MI patients compared to health education alone. The primary outcome is a composite of 1-year cardiovascular death and hospital readmission for cardiovascular cause.

Detailed description: The PIpELINe trial will include older MI patients. All patients aged 65 years and older undergoing coronary angiography because of MI must be screened for eligibility. Patient's eligibility must be assessed after percutaneous revascularization of all lesions considered susceptible of treatment. After verifying inclusion and exclusion criteria and after eligibility is confirmed, written informed consent must be obtained prior to randomization. At the time of the discharge (T0) SPPB test will be performed; in case of a score between 4 and 9, the patient will be evaluated 1-month after discharge at the inclusion visit (T1). If SPPB value is confirmed to be between 4 and 9, randomization will be performed. Key baseline patient characteristics (i.e., inclusion/exclusion criteria, demographics, medical history, details of cardiovascular anatomy and of revascularization, ECG and laboratory test results, echocardiographic data during the index hospitalization) will be recorded on the electronic Case Report Forms (eCRF). All angiographic and echocardiographic data will be collected and forwarded to a core lab for further assessment.

Randomization will be performed during the inclusion visit (T1), 30 days after discharge. Randomization will be performed centrally using an internet-based system. The patient identification number (Patient ID) and the treatment allocation will be assigned by the central randomization system. Patients will be randomized to physical activity group or health education group by a 2:1 allocation. Treatment allocation will be assigned according to a computer-generated randomization list stratified by center. All randomized patients are irrevocably in the study, whether or not they are subsequently found to be eligible, or actually receiving the allocated treatment. Therefore, all patients must be followed until the pre-specified study end date.

The aim of the study is to demonstrate that the proposed multi-domain lifestyle intervention reduces the composite endpoint of cardiovascular death and hospital readmission for cardiovascular cause. The primary endpoint is at 1 year. The follow-up will be extended up to 2 and 3 years.

The protocol includes 3 pre-specified substudies. The possibility to participate in the substudy is left to patient's decision and doesn't preclude the procedures of the main protocol.

* Anxiety and depression: previous studies reported an association between cardiovascular events and a subsequent appearance of mood disorders which could determine a lack in following secondary prevention recommendations. No data is available about these disorders in older adults. In order to assess depression after MI in older patients and the effect of physical activity intervention on mood disorders, this sub-study will be performed.
* Mitochondrial function: in both study groups the mitochondrial functional are investigated starting from blood samples and skin biopsy. Skin biopsy is performed to obtain fibroblasts. In-vitro assessment of the mitochondrial function is done on the fibroblasts of patients. The parameters obtained are related with the effectiveness of physical intervention and with the benefit obtained. A total of at least 30 patients is required.
* Lymphocyte and miRNA activity: taking into account the immunosenescence and the benefits of physical activity on the immune system, this sub-study aims to obtain data regarding T-lymphocyte function in older adults and to assess the effect of physical activity intervention on the function of the different groups of T-lymphocyte. Analyses of physical activity effects on micro ribonucleic acids (miRNAs) are also performed.

Eligibility criteria: Inclusion Criteria:

* Patients ≥65 years
* Hospital admission for myocardial infarction
* Invasive management during index hospitalization including coronary artery angiography (± percutaneous coronary revascularization)
* SPPB value 4-9 at 1-month visit after hospital discharge
* Informed consent

Exclusion Criteria:

1. Multivessel coronary artery disease or left main coronary artery disease candidate to surgical revascularization
2. Planned staged percutaneous coronary intervention (PCI)
3. Non-cardiovascular co-morbidity reducing life expectancy to \< 1 year
4. Any factor precluding 1-year follow-up
5. Severe aortic or mitral disease
6. Ejection fraction \<30%
7. Chronic heart failure New York Heart Association (NYHA) III-IV
8. Severe cognitive impairment (SPMSQ \<4)
9. Impossibility to do physical activity due to physical impairment

Primary outcomes:
measure: Cumulative occurrence of cardiovascular death and hospital readmission for cardiovascular cause
timeFrame: 1-year
Secondary outcomes:
measure: Cumulative occurrence of all-cause death
timeFrame: 1-year
measure: Cumulative occurrence of cardiovascular death
timeFrame: 1-year
measure: Cumulative occurrence of all-cause death
timeFrame: 3-year
measure: Cumulative occurrence of cardiovascular death
timeFrame: 3-year
measure: Cumulative occurrence of hospital readmission for cardiovascular cause
timeFrame: 1-year
measure: Cumulative occurrence of hospital readmission for cardiovascular cause
timeFrame: 3-year
measure: Cumulative occurrence of cardiovascular death and hospital readmission for cardiovascular cause
timeFrame: 3-year
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Medicina dello Sport SSD
state: BO
city: Ferrara
country: Italy
facility: Centro Studi Biomedici applicati allo Sport, Ferrara
state: FE
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto, Piacenza
state: PC
city: Bologna
country: Italy
facility: UO Cardiologia, Ospedale Maggiore
city: Ferrara
country: Italy
facility: Cardiology Unit
city: Lagosanto
country: Italy
facility: Cardiologia Riabilitativa, AUSL d Ferrara
city: Piacenza
country: Italy
facility: Medicina dello Sport, AUSL Piacenza
Study officials:
References:
citation: Tonet E, Raisi A, Zagnoni S, Chiaranda G, Pavasini R, Vitali F, Gibiino F, Campana R, Boccadoro A, Scala A, Canovi L, Amantea V, Matese C, Berloni ML, Piva T, Zerbini V, Cardelli LS, Pasanisi G, Mazzoni G, Casella G, Grazzi G, Campo G. Multi-domain lifestyle intervention in older adults after myocardial infarction: rationale and design of the PIpELINe randomized clinical trial. Aging Clin Exp Res. 2023 May;35(5):1107-1115. doi: 10.1007/s40520-023-02389-9. Epub 2023 Mar 25.