CancerPhase 3ICOS-ONENCT01968200
Prevention of Anthracycline-induced Cardiotoxicity
A Phase 3 study testing Enalapril in people with Cancer, run by European Institute of Oncology at 1 site in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- Enalapril
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 268 participants
- Where
- 1 siteItaly
- Study dates
- Dec 2012to Dec 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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..);;
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: ICOS-ONE - Prevention of Anthracycline-induced Cardiotoxicity: a Multicentre Randomized Trial Comparing Two Therapeutic Strategies.
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.
Read the detailed description
Anthracycline-containing chemotherapy is well known to cause dose-dependent, progressive cardiac damage in particular left ventricular dysfunction evolving to heart failure. The development of cardiac dysfunction, even asymptomatic, leads to the exclusion of cancer patients from effective chemotherapy, with a possible negative impact on their oncologic prognosis. The use of troponins (cTn) during cancer chemotherapy with anthracyclines (AC) allows to identify early cardiac injury before the onset of left ventricular dysfunction, with high predictive value. ACE inhibitors (ACEi) and betablockers (BB) prescribed to cancer patients when, during the course or after the end of a chemotherapy, signs or symptoms of cardiac failure are detected, have been shown to be protective in monocentric studies. Prophylaxis with an ACEi, enalapril and a BB, bisoprolol in patients treated with AC-chemotherapy may allow to reduce the risk of cardiovascular injury, allowing for the completion of the whole scheduled antitumoral treatment.
Sample size According to previous studies from the European Institute of Oncology IEO), an increase of circulating troponin levels is estimated to be 20% in the patients treated with anthracyclines at conventional dosage. 134 patients in each arm (Total sample size of 268 patients) are required to detect a 50% relative risk reduction in the incidence of elevated troponins levels at a 2-sided alpha=0.05 and a 1-beta=0.60, taking into account a 5% drop-out rate. This endpoint will allow to compare the strategy based on prevention (arm 1) with the strategy guided by troponin (arm 2). Given the originality of the proposal and the limited resources, this study will be exploratory in nature, waiting for a larger and adequately powered clinical trial designed to observe significant differences in clinical events.
Safety Tolerability of enalapril, valsartan and bisoprolol has been proven over several years and in broad populations of cardiac patients, not only with heart failure, but also at cardiovascular risk in the absence of signs or symptoms of HF. Specific unwanted effects in cancer patients are not expected, based on previous experiences. Special care should be taken to avoid profound hypotension induced by enalapril, valsartan and bisoprolol in these patients. Serious Adverse Events (SAEs) ad Suspected and Unsuspected Serious Adverse Reactions (SUSARs) will be collected and treated appropriately.
- Conditions
- Cancer
- Being tested
- Enalapril
- Keywords
- cancer, chemotherapy, anthracyclines
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnalaprilDrug
Also called naprilene
Naprilene 5 mg tablets; Dosage: 2.5 to 10 mg/12h Duration of treatment: up to end of follow up
| Study group | Role | What they receive |
|---|---|---|
| Enalapril concomitant | Experimental | Enalapril started concomitantly to AC-containing treatments Receives: Drug: Enalapril |
| Enalapril after injury | Experimental | Enalapril prescribed to selected patients showing laboratory evidences of injury after chemotherapy at follow-up visits. Receives: Drug: Enalapril |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 1 year after the completion of the anthracyclines containing chemotherapy.
Secondary outcomes (3)
admissions to hospital for cardiovascular causes,
to assess whether enalapril administered concomitantly to AC-containing treatments can reduce admissions to hospital for cardiovascular causes
Measured: up to 3 years after the completion of the anthracyclines containing chemotherapy.
cardiovascular deaths
to assess whether enalapril administered concomitantly to AC-containing treatments can reduce cardiovascular deaths
Measured: up to 1 year after the completion of the anthracyclines containing chemotherapy.
occurrence of hypo- or hyperkinetic arrhythmias
to assess whether enalapril administered concomitantly to AC-containing treatments can reduce new occurrence of hypo- or hyperkinetic arrhythmias
Measured: up to 1 year after the completion of the anthracyclines containing chemotherapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2013 (estimated)
- Study startDec 2012
- Primary completionDec 2019
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by European Institute of OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 268 participants (estimated)
Sponsor and investigators
- Lead sponsor
- European Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Carlo Cipolla, MD, Principal investigator, European Institute of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01968200
- Sponsor's protocol ID
- IEO S701/412
- Other IDs
- 2012-002248-26
- Acronym
- ICOS-ONE
- Status last verified
- Jun 2023
- First submitted
- 29 Jul 2013
- Last updated
- 28 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ICOS-ONE - Prevention of Anthracycline-induced Cardiotoxicity: a Multicentre Randomized Trial Comparing Two Therapeutic Strategies.
- ClinicalTrials.gov ID
- NCT01968200
- Acronym / sponsor ID
- ICOS-ONE / IEO S701/412
- Conditions
- Cancer
- Keywords
- cancer, chemotherapy, anthracyclines
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 268 participants (estimated)
- Lead sponsor
- European Institute of OncologyUniversity, hospital or other
- Study start
- Dec 2012 (actual)
- Primary completion
- Dec 2019 (actual)
- Study completion
- Dec 2023 (estimated)
- First posted
- 23 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Anthracycline-containing chemotherapy is well known to cause dose-dependent, progressive cardiac damage in particular left ventricular dysfunction evolving to heart failure. The development of cardiac dysfunction, even asymptomatic, leads to the exclusion of cancer patients from effective chemotherapy, with a possible negative impact on their oncologic prognosis. The use of troponins (cTn) during cancer chemotherapy with anthracyclines (AC) allows to identify early cardiac injury before the onset of left ventricular dysfunction, with high predictive value. ACE inhibitors (ACEi) and betablockers (BB) prescribed to cancer patients when, during the course or after the end of a chemotherapy, signs or symptoms of cardiac failure are detected, have been shown to be protective in monocentric studies. Prophylaxis with an ACEi, enalapril and a BB, bisoprolol in patients treated with AC-chemotherapy may allow to reduce the risk of cardiovascular injury, allowing for the completion of the whole scheduled antitumoral treatment.
Sample size According to previous studies from the European Institute of Oncology IEO), an increase of circulating troponin levels is estimated to be 20% in the patients treated with anthracyclines at conventional dosage. 134 patients in each arm (Total sample size of 268 patients) are required to detect a 50% relative risk reduction in the incidence of elevated troponins levels at a 2-sided alpha=0.05 and a 1-beta=0.60, taking into account a 5% drop-out rate. This endpoint will allow to compare the strategy based on prevention (arm 1) with the strategy guided by troponin (arm 2). Given the originality of the proposal and the limited resources, this study will be exploratory in nature, waiting for a larger and adequately powered clinical trial designed to observe significant differences in clinical events.
Safety Tolerability of enalapril, valsartan and bisoprolol has been proven over several years and in broad populations of cardiac patients, not only with heart failure, but also at cardiovascular risk in the absence of signs or symptoms of HF. Specific unwanted effects in cancer patients are not expected, based on previous experiences. Special care should be taken to avoid profound hypotension induced by enalapril, valsartan and bisoprolol in these patients. Serious Adverse Events (SAEs) ad Suspected and Unsuspected Serious Adverse Reactions (SUSARs) will be collected and treated appropriately.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Enalapril concomitant | Experimental | Drug: EnalaprilEnalapril started concomitantly to AC-containing treatments |
| Enalapril after injury | Experimental | Drug: EnalaprilEnalapril prescribed to selected patients showing laboratory evidences of injury after chemotherapy at follow-up visits. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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%
Key exclusion criteria (15 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnalaprilAlso: naprileneNaprilene 5 mg tablets; Dosage: 2.5 to 10 mg/12h Duration of treatment: up to end of follow up | Drug | Enalapril after injury, Enalapril concomitant |
Primary outcome
the occurrence of cTn elevation above the threshold in use at the local laboratory, at any time during the study
Time frame: up to 1 year after the completion of the anthracyclines containing chemotherapy.
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.
3 secondary outcomes
admissions to hospital for cardiovascular causes,
Time frame: up to 3 years after the completion of the anthracyclines containing chemotherapy.
cardiovascular deaths
Time frame: up to 1 year after the completion of the anthracyclines containing chemotherapy.
occurrence of hypo- or hyperkinetic arrhythmias
Time frame: up to 1 year after the completion of the anthracyclines containing chemotherapy.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carlo Cipolla, MD principal investigator
European Institute of Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Enalapril in people with Cancer, run by European Institute of Oncology at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the occurrence of cTn elevation above the threshold in use at the local laboratory, at any time during the study (time frame: up to 1 year after the completion of the anthracyclines containing chemotherapy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2023.