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

Phase 3

Recruiting

• Conditions: Non-small Cell Lung Cancer; Cardiovascular Complication
• Interventions: Drug: Multiple cardiovascular drugs related to "Golden Triangle"

• Registration Number: NCT04980716
• Lead Sponsor: Sun Yat-sen University

Brief Summary

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

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, before radiotherapy, Mid-radiotherapy, 2 months after the completion of radiotherapy, every 6 months thereafter for up to 2 years post-radiotherapy.

Study Timeline

• Study Start: 2021-06-01
• Study First Submitted: 2021-07-24
• Study First Submitted QC: 2021-07-24
• Study First Posted: 2021-07-28
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-21
• Last Update Posted: 2024-07-23
• Primary Completion: 2026-01-31
• Study Completion: 2026-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 524

Inclusion Criteria

1. 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;
2. Plan to receive radical radiotherapy and chemotherapy ± immunotherapy;
3. Male or female between 18 and 75 years old;
4. Life expectancy ≥ 12 weeks;
5. The World Health Organization (WHO) PS score is 0 or 1;
6. 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;
7. A signed informed consent form is required before proceeding with any step in the research;
8. There is an abnormality in the initial cardiac output index.

Exclusion Criteria

1. PS score 2-4;
2. 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;
3. Unstable angina or myocardial infarction occurred in the past month;
4. Arrhythmia that has not been controlled and can cause symptoms or abnormal hemodynamics;
5. Active endocarditis;
6. Symptomatic severe aortic stenosis;
7. Heart failure that has not been controlled;
8. Acute pulmonary embolism, pulmonary infarction or low thrombosis (artery or vein) formation;
9. Suspected or confirmed aortic dissection;
10. Uncontrolled bronchial asthma;
11. Pulmonary edema;
12. Fingertip blood oxygen saturation at rest ≤85%;
13. Acute non-cardiopulmonary diseases (such as infection, renal failure, thyrotoxicosis, etc.) that may affect sports performance or aggravate due to exercise;
14. Mental disorders make it impossible to cooperate.
15. Patients for whom drug intervention is clearly recommended according to the 2022 edition of the European Society of Cardiology Guidelines on Cardio-Oncology.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
The early intervention group	Multiple cardiovascular drugs related to "Golden Triangle"	The early intervention group: evaluation and intervention based on impedance cardiography results at multiple timepoints. Specific intervention measures include: 1. cardiovascular drug treatment: based on the increase and decrease of the "Golden Triangle" 1. ACEI, perindopril tert-butyrate 4mg qd 2. β receptor antagonist, metoprolol succinate 47.5mg qd 3. Spironolactone 20mg qd 4. Drugs to improve myocardial metabolism: trimetazidine hydrochloride 35 mg bid 5. Other therapeutic drugs include: loop diuretics, ARNI, sinus node If current selection specific inhibitors, statins, antiplatelet aggregation and nitrate drugs, etc. 2. Exercise intervention: exercise prescription based on the initial cardiopulmonary exercise test results.

Primary Outcome Measures

Name	Time	Method
Overall survival	2-year	It was calculated from the first day of treatment to the day of death.
The incidence of grade 2+ cardiotoxicity events	2-year	Culmulative incidence of grade 2+ cardiotoxicity events

Secondary Outcome Measures

Name	Time	Method
Progression-free survival	2-year	From the first day of treatment to the day of progression or the day of death.

Trial Locations

Locations (1)

Sun yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China