Prevention of Anthracycline-induced Cardiotoxicity

NCT01968200 | Unknown Phase 3

• 2 other identifiers: IEO S701/4122012-002248-26
• Study Type: interventional
• Target: 268
• Locations: 1 country
• Sites: 1

Brief Summary

Anthracycline based anti-tumoral therapies are know to develop cardiac damage that could also lead to heart failure. Monocentric studies proved that a treatment with ACE inhibitors (ACEi) and betablockers (BB) during the first elevation of cardiac troponin is able to reduce the incidence of heart failure (HF). ICOS-ONE trial is a multicenter randomized trial comparing two therapeutic strategies. The main objective is to assess whether enalapril started concomitantly to AC-containing treatments, can prevent cardiac toxicity more effectively than when enalapril is prescribed to selected patients showing laboratory evidences of injury after chemotherapy, during follow-up visits in 268 patients.

Conditions

Cancer

Keywords

cancer; chemotherapy; anthracyclines

Outcome Measures

Primary Outcomes (1)

• the occurrence of cTn elevation above the threshold in use at the local laboratory, at any time during the study

  To assess whether enalapril administered concomitantly to anthracyclines (AC) containing treatments can prevent cardiac toxicity more effectively than enalapril prescribed to selected patients showing laboratory evidences of injury after chemotherapy (CT), at follow-up visits. Cardiac toxicity is measured on the basis of cardiac troponin levels.

  up to 1 year after the completion of the anthracyclines containing chemotherapy.

Secondary Outcomes (3)

• admissions to hospital for cardiovascular causes,

  up to 3 years after the completion of the anthracyclines containing chemotherapy.

• cardiovascular deaths

  up to 1 year after the completion of the anthracyclines containing chemotherapy.

• occurrence of hypo- or hyperkinetic arrhythmias

  up to 1 year after the completion of the anthracyclines containing chemotherapy.

Study Arms (2)

Enalapril concomitant

EXPERIMENTAL

Enalapril started concomitantly to AC-containing treatments

Drug: Enalapril

Enalapril after injury

EXPERIMENTAL

Enalapril prescribed to selected patients showing laboratory evidences of injury after chemotherapy at follow-up visits.

Drug: Enalapril

Interventions

Enalapril DRUG

Naprilene 5 mg tablets; Dosage: 2.5 to 10 mg/12h Duration of treatment: up to end of follow up

Also known as: naprilene

Enalapril after injury; Enalapril concomitant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with diagnosis of cancer and indication for first- and second-line therapy with anthracyclines
• Age ≥18years
• Serum creatinine\<177µmol/L(2mg/100mL)
• Systolic blood pressure ≥100 mmHg and ≤170 mmHg
• Left ventricular ejection fraction (VEF) \>50%
• Written informed consent.
• Life expectancy of at least 12 months

You may not qualify if:

• Patients with history or clinical/instrumental evidences of heart failure
• Patients with history or clinical/instrumental evidences of ischemic heart disease;
• Patients with blood troponin levels higher than the cut-off suggested by the manufacturer before starting cancer CT;
• Systolic blood pressure\<100 mmHg;
• Heart rate\<50 bpm;
• Prior malignancy requiring potentially cardiotoxic chemotherapy (e.g. anthracyclines, trastuzumab..);;
• Uncontrolled hypertension defined as systolic blood pressure\>170 mmHg;
• Treatment with ACEi, ARB or BB within 4 weeks prior to study start;
• Known intolerance to enalapril, except for cough;
• Planned treatment with dexrazoxane;
• Participation in another experimental drug trial within 4 weeks prior to study start;
• Non-cooperative behaviour or suspected poor compliance;
• Psychiatric disorders or conditions that might impair the ability to give informed consent;
• Pregnancy or breast feeding;
• Scheduled mediastinal radiotherapy.

Sponsors & Collaborators

• European Institute of Oncology: lead

Study Sites (1)

European Institute of Oncology

Milan, Italy

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Enalapril

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Carlo Cipolla, MD

  European Institute of Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2013
• First Posted: October 23, 2013
• Study Start: December 1, 2012
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2023
• Last Updated: June 28, 2023

Record last verified: 2023-06

Locations

IT (1)