Early Specialized Cardiovascular Intervention Based on Impedance Cardiography in Locally Advanced Non-small Cell Lung Cancer Patients

Study Overview
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Brief Summary
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This is a prospective, randomized, controlled, multi-center phase III clinical trial that intends to evaluate the role of early cardiovascular intervention based on impedance cardiography in patients with locally advanced non-small cell lung cancer receiving radical radiochemotherapy±immunotherapy.

Detailed Description
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This is a prospective, randomized, controlled, multi-center phase III clinical trial that intends to evaluate the role of early cardiovascular intervention based on impedance cardiography in patients with locally advanced non-small cell lung cancer receiving radical radiochemotherapy±immunotherapy. The participants were 1:1 randomized to the intervention group and the control group. The intervention group will receive cardiovascular evaluation and intervention at multiple timepoints throughout treatment and follow-up, while the control group will be under observation unless severe cardiovascular events happen. The evaluation and intervention timepoints include: Before neoadjuvant therapy (no intervention time point for those who do not receive neoadjuvant therapy), before the first course of radiotherapy, 3-4 weeks after the first course of radiotherapy, 2 months after the second course of radiotherapy, 8 months after the second course of radiotherapy, 14 months after the second course of radiotherapy .

Official Title
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Early Specialized Cardiovascular Intervention Based on Impedance Cardiography in Locally Advanced Non-small Cell Lung Cancer Patients Who Receiving Radical Concurrent Chemoradiotherapy and Immunotherapy: a Prospective, Randomized Controlled, Multicenter Phase III Clinical Trial.

Conditions
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Non-small Cell Lung Cancer, Cardiovascular Complication

Intervention / Treatment
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* Drug: Multiple cardiovascular drugs related to Golden Triangle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: It is diagnosed as non-small cell lung cancer by pathological examination or cytological examination; it is assessed as locally advanced, unresectable stage III non-small cell lung cancer by imaging; Plan to receive radical radiotherapy and chemotherapy ± immunotherapy; Male or female between 18 and 75 years old; Life expectancy ≥ 12 weeks; The World Health Organization (WHO) PS score is 0 or 1; Organ and bone marrow function meet the following conditions: Forced expiratory volume per second (FEV1) ≥1000 ml; absolute neutrophil count ≥1.5×10^9/L; platelets ≥100×10^9/L; hemoglobin ≥90 g/L ; Serum creatinine clearance calculated according to the Cockcroft-Gault formula ≥50 mL/min (Cockcroft and Gault 1976); serum bilirubin ≤1.5 times the upper limit of normal (ULN); alanine aminotransferase and aspartate aminotransferase ≤2.5 times ULN; A signed informed consent form is required before proceeding with any step in the research; There is an abnormality in the initial cardiac output index. Exclusion Criteria: PS score 2-4; Organ function impairment: FEV1 <1000ml; absolute neutrophil count <1.5×10^9/L; platelets <100×10^9/L; hemoglobin <90 g/ L; Serum creatinine clearance calculated according to Cockcroft-Gault formula <50 mL/min; serum bilirubin>1.5 times ULN; alanine aminotransferase and aspartate aminotransferase>2.5 times ULN; Unstable angina or myocardial infarction occurred in the past month; Arrhythmia that has not been controlled and can cause symptoms or abnormal hemodynamics; Active endocarditis; Symptomatic severe aortic stenosis; Heart failure that has not been controlled; Acute pulmonary embolism, pulmonary infarction or low thrombosis (artery or vein) formation; Suspected or confirmed aortic dissection; Uncontrolled bronchial asthma; Pulmonary edema; Fingertip blood oxygen saturation at rest ≤85%; Acute non-cardiopulmonary diseases (such as infection, renal failure, thyrotoxicosis, etc.) that may affect sports performance or aggravate due to exercise; Mental disorders make it impossible to cooperate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The early intervention group<br>The early intervention group: evaluation and intervention based on impedance cardiography results at multiple timepoints. Specific intervention measures include: cardiovascular drug treatment: based on the increase and decrease of the Golden Triangle ACEI, perindopril tert-butyrate 4mg qd β receptor antagonist, metoprolol succinate 47.5mg qd Spironolactone 20mg qd Drugs to improve myocardial metabolism: trimetazidine hydrochloride 35 mg bid Other therapeutic drugs include: loop diuretics, ARNI, sinus node If current selection specific inhibitors, statins, antiplatelet aggregation and nitrate drugs, etc. Exercise intervention: exercise prescription based on the initial cardiopulmonary exercise test results. | Drug: Multiple cardiovascular drugs related to Golden Triangle<br>* Based on impedance cardiography results at each timepoints, cardiovascular drug treatment and exercise plan will be given in the intervention group.<br>|
| No Intervention: The control group<br>This group will be under observation. When cardiovascular events (including ischemic cardiomyopathy, heart failure, arrhythmia requiring treatment, pericardial disease requiring treatment, valvular disease, etc.) happen, a cardiovascular specialist assessment and intervention will be given. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | It was calculated from the first day of treatment to the day of death. | 2-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of cardiotoxicity events | Cumulative incidence of ≥ Grade 3 cardiotoxicity events | 2-year | 
| Progression-free survival | From the first day of treatment to the day of progression or the day of death. | 2-year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small Cell Lung Cancer, Cardiovascular Intervention, Impedance Cardiography, Cardiovascular Event