Multidimensional Approach for COPD and High Complexity | NCT04986332

NCT04986332

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

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Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Detailed Description

MACH Study investigators designed a trial to evaluate in high complexity subjects (at least 2 chronic diseases):

in the COPD cohort, the impact of a multidimensional approach involving global therapeutic remodeling (re-assessing and therapeutic optimization of the whole burden of chronic pathologic conditions) plus a 24-weeks moderate intensity physical activity program on: number of total and severe exacerbations; number of total and COPD/related hospitalizations; quality of life; survival over a 36 months follow-up period;
to establish whether a higher index of comorbidity and polypharmacy is independently associated with a worst clinical severity of COPD, an increased risk of exacerbations and a reduced survival;
the role played by specific clinical-laboratory markers of comorbidity (blood iron profile, hemochromocytometric parameters, renal function, blood pressure profile, glycemic compensation, Body Mass Index, lipid profile) and specific multidimensional tests in identifying COPD patients with higher clinical risk of rapid disease decline and/or higher risk of exacerbations and COPD-related hospitalizations;
to establish the role of Heart Failure as the most impactful comorbidity of COPD: assess the incidence rate and the relative risk of total/severe exacerbation and the incidence rate and the relative risk of total/COPD-related hospitalizations in Heart Failure/COPD patients over a 36-months follow-up period;
at the enrollment time (zero time) and after 12, 24 and 36 months, circulating levels of several systemic inflammation biomarkers. Correlate their variation over time with the comorbidity indexes, global pharmacological therapeutic redefinition and lifestyle intervention centered on 24-weeks physical activity program;
at the enrollment time (zero time) and after 12, 24 and 36 months, plasma levels of the main miRNAs involved in the COPD pathogenesis. Correlate their variation over time with the comorbidity indexes, global pharmacological therapeutic redefinition and lifestyle intervention centered on 24-weeks physical activity program;
at the enrollment time (zero time) and after 12, 24 and 36 months, plasma levels of the main myokines currently associated with the systemic effects of physical activity, correlating their baseline concentration to clinical-anthropometric parameters and type and number of chronic diseases and their variation over time in relation to the global pharmacological therapeutic redefinition and the 24-weeks physical activity program;

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
GROUP "COPD"	Experimental	100 participants, 50 males and 50 females with COPD and multiple chronic conditions	Behavioral: Physical activity program Other: Global therapeutic remodeling
GROUP "HF"	Active Comparator	100 participants, 50 males and 50 females with HF and multiple chronic conditions	Behavioral: Physical activity program Other: Global therapeutic remodeling
GROUP "HEALTHY PARTICIPANTS"	Active Comparator	100 healthy participants or "control group" which will be compared to Group A and Group B by age and sex	Behavioral: Physical activity program Other: Global therapeutic remodeling

Name	Type	Description	Arm Group Labels	Other Names
Physical activity program	Behavioral	24-weeks moderate-intensity physical activity program	GROUP "COPD" GROUP "HEALTHY PARTICIPANTS" GROUP "HF"

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Cumulative incidence of COPD exacerbation of Group "COPD"	The effect of a 24-weeks moderate-intensity physical activity program and re-assessing and therapeutic optimization of the whole burden of chronic pathologic conditions on the number of COPD exacerbation per year. The severity of COPD exacerbation will be assessed as follow: Mild: treated with short acting bronchodilators only; Moderate: treated with bronchodilators and/or oral corticosteroids; Severe: patient requires hospitalization or visits the emergency room;	Baseline to 12 months
Cumulative incidence of COPD exacerbation of Group "COPD"	The effect of a 24-weeks moderate-intensity physical activity program and re-assessing and therapeutic optimization of the whole burden of chronic pathologic conditions on the number of COPD exacerbation per year. The severity of COPD exacerbation will be assessed as follow: Mild: treated with short acting bronchodilators only; Moderate: treated with bronchodilators and/or oral corticosteroids; Severe: patient requires hospitalization or visits the emergency room;	Baseline to 24 months
Cumulative incidence of COPD exacerbation of Group "COPD"	The effect of a 24-weeks moderate-intensity physical activity program and re-assessing and therapeutic optimization of the whole burden of chronic pathologic conditions on the number of COPD exacerbation per year. The severity of COPD exacerbation will be assessed as follow: Mild: treated with short acting bronchodilators only; Moderate: treated with bronchodilators and/or oral corticosteroids; Severe: patient requires hospitalization or visits the emergency room;	Baseline to 36 months
Cumulative incidence of hospitalization for pneumonia of Group "COPD"	The effect of a 24-weeks moderate-intensity physical activity program and re-assessing and therapeutic optimization of the whole burden of chronic pathologic conditions on the number of hospitalization per year for pneumonia. Pneumonia will be ascertain clinically and/or radiologically.

Secondary Outcomes

Measure	Description	Time Frame
Change over time from baseline on the circulating levels of Interleukin-6 (IL-6) (pg/mL) of Group "COPD"	The effect of a 24-weeks moderate-intensity physical activity program and re-assessing and therapeutic optimization of the whole burden of chronic pathologic conditions on the circulating levels of IL-6 (pg/mL) of Group "COPD"	Baseline to post-interventions at 12 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Provide signed and dated informed consent form;
Willing to comply with all study procedures and be available for the duration of the study;
COPD diagnosis (according to "Global Initiative for Chronic Obstructive Lung Disease" (GOLD) 2020 Guidelines) or HF diagnosis (according to European Society of Cardiology (ESC) 2016 Guidelines for the diagnosis and treatment of acute and chronic heart failure);
Diagnosis at least two other chronic diseases, in addition to COPD (Group A) or HF (Group B). If COPD and HF diagnoses are both present in the same subject, COPD or HF will be considered as the index pathology in view of the clinical relevance and ergo, the participant will be included in the group A or in the group B;
Healthy subjects exclusively for Group C;

Chronic diseases are considered the following:

Type 1 or Type 2 Diabetes mellitus
Essential hypertension
Chronic Kidney Disease Stage 3b or worst (Glomerular Filtration Rate < 44 mL/min/1.73 m^2 estimated through the Cockcroft-Gault formule)
Chronic Anemia of moderate level of lower (Haemoglobin levels ≤10.9 g/dl) according to World Health Organization (WHO) classification
Chronic liver disease (every etiology)
Obesity (Body Mass Index ≥ 30)

Exclusion Criteria:

Active cigarette smoking;
Need for continuous supportive oxygen therapy, regardless of the flow required;
Distance covered during the 6 minutes walking test (6MWT) < 300 meters;
Unstable angina pectoris or angina pectoris at rest, a history of cardiac arrest, "New York Heart Association" (NYHA) Class III or IV congestive heart failure or severe left ventricular systolic dysfunction (EF <30%), acute myocarditis, pericarditis or hypertrophic myocardiopathy, clinically significant aortic stenosis, cardiac defibrillator, heart transplant, history of aortic aneurysm of at least 7 cm in diameter or aortic aneurysm repair;
Uncontrolled or partially controlled asthma despite optimal treatment; Sleep apnea syndrome; history of pulmonary fibrosis;
Recent acute cardiac or cerebral event in the last six months;
Child-Pugh B/C cirrhosis;
Body Mass Index ≥ 35;
Evidence of any arrhythmia (uncontrolled atrial fibrillation (heart rate of 100 beats per minute or more), left bundle branch block or cardiac pacemaker, etc.) that contraindicates or makes unsafe the fulfilment of the regular physical activity program, assessed on the basis of the clinical history, documentation presented and clinical and instrumental evaluation carried out at the time of enrollment;
Resting heart rate less than 45 beats per minute or greater than 100 beats per minute;
History of uncontrolled or partially controlled high blood pressure despite optimal treatment;
Regular physical activity practice (the level of habitual physical activity practiced will be ascertained by administering specific questionnaires. Only sedentary participants will be eligible);
Inability to perform the 24-weeks physical activity program for any cause (muscle, joint, respiratory, neurological, vascular, diabetes complications);
Any acute or chronic disease, already known at the time of enrollment, capable of altering systemic inflammation biomarkers and cytokine profile (e.g. sepsis, infections, immune-rheumatological diseases, hematological diseases, etc.).
Any muscle condition, inflammatory or not, capable of altering muscular myokines' release (polymyositis, rheumatic polymyalgia, fibromyalgia);
Acute bleeding at the time of enrollment or any anemia that would have been required urgent transfusion within the past three months;
Solid or hematological neoplasia under active (at the time of enrollment) or recent (ended less than 6 months earlier) chemo-radiotherapy treatment at the time of enrollment;
Current diagnosis of schizophrenia, other psychotic disorders or bipolar disorder uncontrolled or partially controlled despite optimal treatment;
Self-report of alcohol or substance abuse within the past twelve months, current consumption of more than 14 alcoholic drinks per week, and/or current acute treatment or rehabilitation program for these problems;
Severe cognitive impairment or anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study;
Conditions not specifically mentioned above that may serve as criteria for exclusion at the discretion of the PI and study staff;

ID	Term
D029424	Pulmonary Disease, Chronic Obstructive
D006333	Heart Failure
D002908	Chronic Disease

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D020969	Disease Attributes