Cardiovascular Toxicity Induced by Antitumoral Drugs: Risk Assessment and Early Diagnosis. CARDIOTOX Registry

The study is multicenter, post-authorization, observational and ambispective

Study Overview

• Status: Unknown
• Conditions: Cardiovascular Toxicity Induced by Antitumoral Drugs

Detailed Description

Cardiovascular toxicity produced by antitumoral drugs has a considerable impact in life wellness and prognosis of cancer patients, which can imply the suspension of the desired antitumoral treatment or even risk the patient´s life. The development of a risk score for these patients, as well as specific methodology for early detection of cardiotoxicity would therefore be a great outcome to trigger new strategies for the monitoring of these patients. Currently there is a lack of a clinical score to predict cardiotoxicity risk. Therefore, there is an urgent need to identify new myocardial injury biomarkers and novel imaging parameters for measuring ventricular function that would increase the sensitivity of the traditional methods used for the early detection of cardiotoxicity.

The objectives of the present study are the following:

• Identify the factors related with cardiotoxicity risk produced by antitumoral drugs.
• Assess the utility of clinical, biological and functional parameters for the early detection of cardiotoxicity produced by antitumoral drugs.

The study is a multicenter one, observational and ambispective. We will include all the patients assessed by the Oncology and Haematology Departments in each participant hospital that are about to initiate or are undergoing chemotherapy with any of the drugs specified in the study protocol. Patients will be monitorized during the treatment, undergoing an echocardiography study and a blood sample collection in each clinical timepoint. All these parameters will hopefully shed some light for the development of a clinical risk score as well as identifying new early biomarkers for cardiotoxicity.

The initial follow-up in this phase of the study will be 2 years

• Study Type: Observational
• Enrollment (Anticipated): 3400

Contacts and Locations

• Study Contact: Name: Jose Luis Lopez-Sendon; Phone Number: +34 639148765; Email: jlopezsendon@gmail.com
• Study Contact Backup: Name: Maria Torrente; Phone Number: (+34) 607684323; Email: maria.torrente@idipaz.es

Study Locations

• Spain
  • Madrid, Spain, 28046
    • Recruiting
    • La Paz University Hospital
    • Contact: Jose Luis Lopez-Sendon; Phone Number: +34 639148765; Email: jlopezsendon@gmail.com
    • Contact: Maria Torrent; Phone Number: (+34) 607684323; Email: maria.torrente@idipaz.es
    • Principal Investigator: Jose Luis Lopez-Sendon
    • Sub-Investigator: Elena RAmirez
    • Sub-Investigator: Jaime Feliu
    • Sub-Investigator: Enrique Espinosa
    • Sub-Investigator: Antonio Buño
    • Sub-Investigator: Miguel Canales
    • Sub-Investigator: Mar Moreno
    • Sub-Investigator: Teresa Lopez
    • Sub-Investigator: Maria Torrente
    • Sub-Investigator: Olaia Rodriguez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A case is defined as a patient on treatment (started or programmed, regardless of previous treatments or prior radiotherapy) with the following target antineoplastic agents:

• Alkylating agents
• Antimicrotubule agents
• Vinca alkaloids
• Monoclonal Antibodies
• Antimetabolites
• Anthracyclines
• Angiogenesis inhibitors
• Interleukins
• Small molecule tyrosine kinase inhibitors
• Other antineoplastic agents

Description

Inclusion Criteria:

• Patients> 18 years with indicated antitumor chemotherapy.
• Estimated survival ≥ 6 months
• No oxygen dependence
• No contraindication for taking the study target antitumor agents.
• No exclusion of patients with risk factors or previous heart disease.
• No exclusion of patients with previous cancer, previous antitumor treatment, current antitumor treatment, previous or current radiotherapy.
• No exclusion of patients with previous cardiovascular toxicity

Exclusion Criteria:

• No exclusion criteria.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patient under study condition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CARDIOTOXICITY DEVELOPMENT RISK SCORE	Risk of cardiovascular toxicity by antitumoral agents is multifactorial.; Clinical heart failure; Asymptomatic ventricular dysfunction; Elevated biomarkers; Severe arrhythmias; Myocardial ischemia; Other cardiac events	21 days, 3 months, 6 months, 1 year, 1.5 years and 2 years
change in EARLY DETECTION OF CARDIOTOXICITY	Early recognition of cardiotoxicity can help determine whether to continue treatment with a particular type of drug and set up preventive treatments.; Demographic variables for study inclusion; Clinical symptoms of cardiac disease; EKG; Transthoracic echocardiogram; Biological markers: Troponin I (cTnI), NTproBNP; Oncological variables: Diagnosis and cancer location, Drugs	21 days, 3 months, 6 months, 1 year, 1.5 years and 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of cardiovascular toxicity in its different forms	Cardiotoxicity severity: Mild: asymptomatic, no hospitalization needed; Severe: requires admission or specific treatment initiated for this reason	2 years
Incidence of cardiovascular toxicity in relation to the cumulative dose	Heart failure; Asymptomatic ventricular dysfunction; Myocardial Ischemia; Severe arrhythmias; Other cardiac pathology	21 days, 3 months, 6 months, 1 year, 1.5 years and 2 years
•Incidence of cardiovascular toxicity in relation to the kind of antitumor agent	Heart failure; Asymptomatic ventricular dysfunction; Myocardial Ischemia; Severe arrhythmias; Other cardiac pathology	21 days, 3 months, 6 months, 1 year, 1.5 years and 2 years
•Analyze the sensitivity and specificity of EKG changes regarding new changes in biomarkers, clinical and echocardiographic parameters	- EKG	21 days, 3 months, 6 months, 1 year, 1.5 years and 2 years
Analyze whether alterations of biological markers predate clinical, echocardiographic and functional parameters	Troponin I; NT-proBNP	21 days, 3 months, 6 months, 1 year, 1.5 years and 2 years
Compare the effectiveness of early identification of cardiovascular toxicity of high-sensitivity troponin (troponin T) compared to a conventional troponin	Troponin I (cTn I); Troponin Thigh sensitivity (cTnhs)	21 days, 3 months, 6 months, 1 year, 1.5 years and 2 years
Define the sensitivity and specificity of the left ventricle ejection fraction in the detection of cardiovascular toxicity	Telediastolic volume left ventricle; Telesystolic volume right ventricle; Ejection fraction left ventricle; Size of left atrium; Size right atrium; Mitral valve disease; Tricuspid valve disease; Pericardial overflow	21 days, 3 months, 6 months, 1 year, 1.5 years and 2 years
• Define the sensitivity and specificity of new ventricular function parameters in cardiovascular toxicity screening.	- Longitudinal global strain	21 days, 3 months, 6 months, 1 year, 1.5 years and 2 years
Economic analysis derived from the diagnostic strategy with biomarkers versus echocardiography.	Economic analysis comparing efficacy of biomarkers versus echocardiography	2 years

Collaborators and Investigators

• Sponsor: Instituto de Investigación Hospital Universitario La Paz
• Investigators: Principal Investigator: Jose Luis Lopez-Sendon, La Paz University Hospital- Chief of Cardiology Department

Publications and helpful links

General Publications

• Caro-Codon J, Lopez-Fernandez T, Alvarez-Ortega C, Zamora Aunon P, Rodriguez IR, Gomez Prieto P, Buno Soto A, Canales Albendea M, Albaladejo A, Mediavilla G, Feliu Batlle J, Rodriguez Fraga O, Martinez Monzonis A, Gonzalez-Costello J, Serrano Antolin JM, Cadenas Chamorro R, Gonzalez-Juanatey JR, Lopez-Sendon J; CARDIOTOX registry investigators. Cardiovascular risk factors during cancer treatment. Prevalence and prognostic relevance: insights from the CARDIOTOX registry. Eur J Prev Cardiol. 2022 May 6;29(6):859-868. doi: 10.1093/eurjpc/zwaa034.

Helpful Links

• Web site of the study

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: January 10, 2014
• First Submitted That Met QC Criteria: January 15, 2014
• First Posted (Estimate): January 17, 2014

Study Record Updates

• Last Update Posted (Estimate): January 17, 2014
• Last Update Submitted That Met QC Criteria: January 15, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: GECAME-2010-01