EndocarditisNCT03411499
Stroke-free Survival Comparison Between Early Surgery and Conventional Therapy in Left Infective Endocarditis
A study testing Early surgery and Conventional therapy in people with Endocarditis, run by Maria Vittoria Hospital at 1 site in Italy.
Trial summary
The purpose of the EARLY study is to evaluate the efficacy and effectiveness of early surgery in patients with Infective Endocarditis (IE). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Endocarditis
- What is being tested?
- Early surgery and Conventional therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteItaly
- Study dates
- 22 Dec 2017to 14 Dec 2020
- Phase
- Interventional
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Left-sided Infective Endocarditis (IE) according to modified Duke criteria, fulfilling at least one of the following features:
- IE on native or prosthetic valve with severe mitral or aortic valve regurgitation, without heart failure;
- IE on native or prosthetic valve, during the first week of antibiotic therapy, have very large (15-30 mm) or large (>10mm), mobile isolated vegetations due to Staphylococcus aureus, Streptococcus bovis, HACEK or Abiotrophia, without any other indication for surgery;
- IE on native or prosthetic valve with severe valve regurgitation without heart failure and with large vegetations (> 10 mm) and Euroscore I 5-19;
- IE on native or prosthetic valve with moderate o moderate-severe valve regurgitation with large vegetations (> 10 mm)
- IE on prosthetic valve due to Staphylococcus aureus or gram negative non HACEK microorganisms.
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- Compliance to study treatments
- Euroscore I <20
- Informed consent signature
Who cannot join
- Patients with right-side IE and IE on a cardiac device
- Patients with IE and:
- heart failure , refractory pulmonary oedema, cardiogenic shock or untreatable heart failure
- fistula involving cardiac chambers or pericardium
- persistent heart failure or unstable echocardiographic signs or poor haemodynamic tolerance
- uncontrolled local infection (abscess, pseudoaneurism, fistula, increase in size vegetations)
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- fever and positive blood cultures lasting >7 days
- fungal IE or other multi-resistant microorganisms
- large vegetations (> 10 mm) after embolic event
- large vegetations (> 10 mm) and other predictors of complicated course (heart failure, abscess)
- vegetations >30 mm
Trial locations and contacts
1 site in 1 country.
Italy1 site
SC Cardiochirurgia U - AOU Città della Salute e della Scienza di Torino - PO Molinette
Torino, 10126
About this study
Official title: Stroke-free Survival Comparison Between Early Surgery and Conventional Therapy in Left Infective Endocarditis - A Multicenter Partially Randomized Preference Trial (EARLY Study)
The purpose of the EARLY study is to evaluate the efficacy and effectiveness of early surgery in patients with Infective Endocarditis (IE).
Read the detailed description
Infective endocarditis (IE) is a relatively rare disease and has a high in-hospital mortality (15-30%) and morbidity due to complications like embolic events, especially in the central nervous system, and heart failure. International guidelines give indications on the optimal timing for surgery, and they strongly recommend early surgery for patients in the active phase of IE with acute cardiac complications (e.g., acute heart failure, uncontrolled infection, and persistent large vegetations after an embolic event). However, at present there is no clear evidence supporting the effectiveness of early surgery or indicating the best time to perform surgery, especially in patients without such conditions. Primary objective of the study is to evaluate whether, in patients with IE and no emergency surgery indication, an early surgical strategy (performed within 72 hours from IE diagnosis) is more effective than conventional therapy in terms of 1-year stroke-free survival. Secondary objectives are: overall survival, risk of embolic, risk of strokes, event-free survival, IE relapse, heart failure, length of hospital stay, hospital re-admission and hospitalization days, strategy compliance, quality of life and health care costs.
This study design consist of a two-arm, open-label, multicenter randomized controlled trial, but patients who decline to be randomized and prefer a certain therapy strategy will be treated according to best practice and included into a prospective observational study after given informed consent. This parallel constructed observational study will be performed with a maximum of consistency to treatment and observation compared to the Randomized clinical trial (RCT). Patients who agree to the randomized trial will be stratified according to centre and clinical features (prosthetic valve,vegetations, valve regurgitation) and randomized with a 1: 1 ratio to 2 different strategies.
According to O'Brien and Fleming group sequential design with a maximum of two stages and a drop-out rate of 10%, a total of 400 randomized patients (200 per group) are required to detect an increase in the stroke-free survival from 82% to 89.5% (corresponding to an Hazard Ratio=0.56) considering a significance level of 5% and a power of 80% and expecting a risk for mortality or stroke at one year with standard treatment equal to 0.18.
EARLY study may help to demonstrate early surgery impact on the contemporary management of the disease.
- Conditions
- Endocarditis
- Being tested
- Early surgery, Conventional therapy
- Keywords
- Adult, Endocarditis/surgery, Embolism/prevention & control, Cardiovascular Diseases, Costs and Cost Analysis, Quality of life
- Medical subject headings
- Endocarditis, Embolism, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early surgeryProcedure or surgery
Surgery within 72 hours from endocarditis diagnosis
Conventional therapyProcedure or surgery
Delayed surgical intervention or medical treatment according to the current guidelines
| Study group | Role | What they receive |
|---|---|---|
| Early surgery | Experimental | Surgery within 72 hours from endocarditis diagnosis Receives: Procedure: Early surgery |
| Conventional therapy | Active comparator | Medical treatment and a possible delayed surgical intervention according to the current guidelines Receives: Procedure: Conventional therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stroke-free survival
Time from randomization until the first occurrence of stroke or death. Stroke is defined as a focal neurologic deficit, lasting at least 24 hours and is categorized as ischemic, hemorrhagic or of uncertain type.
Measured: 12 months
Secondary outcomes (16)
Overall survival
Time from randomization until death from any cause
Measured: 12 months
In-hospital mortality
Proportion of death during the hospitalization of IE diagnosis
Measured: During follow-up, until discharge from hospital, up to 1 year from randomization date
Embolic event during the hospitalization of IE diagnosis
Proportion of patients with clinical and instrumental diagnosis of embolic events after IE diagnosis during the same hospitalization
Measured: During follow-up, until discharge from hospital, up to 1 year from randomization date
Stroke during the hospitalization of IE diagnosis
Proportion of patients with clinical and instrumental diagnosis of stroke during the hospitalization of IE diagnosis. Stroke is defined as a focal neurologic deficit, lasting at least 24 hours and is categorized as ischemic, hemorrhagic or of uncertain type.
Measured: During follow-up, until discharge from hospital, up to 1 year from randomization date
Heart failure during the hospitalization of IE diagnosis
Proportion of patients with diagnosis of Heart failure during the hospitalization of IE diagnosis.
Measured: During follow-up, until discharge from hospital, up to 1 year from randomization date
Cumulative incidence of stroke
Probability that a patient will have a stroke at 12 months from randomization assuming they do not die from some other cause.
Measured: 12 months
Cumulative incidence of embolic events
Probability that a patient will have an embolic events at 12 months from randomization assuming they do not die from some other cause.
Measured: 12 months
Cumulative incidence of heart failure
Probability that a patients will have a heart failure at 12 months from randomization assuming they do not die from some other cause.
Measured: 12 months
Cumulative incidence of IE relapse
Probability that a patient will have an IE relapse at 12 months from randomization assuming they do not die from some other cause.
Measured: 12 months
Quality of Life using 36-Item Short Form Survey (SF-36)
SF-36 is a generic 36-item questionnaire measuring health-related quality of life (HRQL) composed by 8 subscales. Participants self-report on items that have between 2-6 choices per item using Likert-type responses. Summations of item scores of the same subscale give the subscale scores. Two composite scores, physical component summary (PCS) and mental component summary (MCS), can be derived by a linear combination of the 8 subscales.
The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health.
Both subscales and composite scores are transformed into a range from 0 to 100; zero= worst HRQL, 100=best HRQL.
Measured: 0, 4, 12 months
Quality of Life using EuroQol five dimension (EQ-5D).
Quality of life will be evaluated using EuroQol five dimension (EQ-5D), a patient-completed, multidimensional measure of health related quality of life. The instrument is applicable to a wide range of health conditions and treatments and results in a single index score. The EQ-5D descriptive health profile comprises five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension comprises three levels (no problems, some/moderate problems, extreme problems). A unique EQ-5D health state is defined by combining one level from each of the five dimensions. EQ-5D index values range from -0.38 to 1.00 (Italian utility weights). Higher EQ-5D Index scores represent better health status.
Measured: 0, 4, 12 months
1-year event-free survival
Time from randomization until the first occurrence of one of the following event: , embolic event, IE relapse and heart failure or death.
Measured: 12 months
Cost-effectiveness
Incremental cost-effectiveness ratio calculated as the ratio between difference in costs and difference in Quality Adjusted Life Years, from EQ-5D (QALYs) among the treatment groups, during the first year after randomization
Measured: 12 months
Length of hospitalization
Number of days from the date of the randomization and the discharge date
Measured: During follow-up, until discharge from hospital, up to 1 year from randomization date
Number of hospital readmission for length .of stay within 1 year for any cause
Number of days of hospitalization for any cause from the the date of discharge
Measured: 12 months
Feasibility of early surgery
Ratio between the number of patients randomized to early surgery arm and operated within 72 hours and the number of patients randomized to early surgery arm
Measured: During follow-up, until discharge from hospital, up to 1 year from randomization date
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2018
- Study start22 Dec 2017
- Primary completion14 Dec 2020
- Study completion14 Dec 2020
Why it stopped: Study stopped because of low enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EndocarditisStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Partially Randomized Preference Trial
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maria Vittoria Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Italy
- Responsible party
- Principal investigator, Enrico Cecchi, Maria Vittoria Hospital
- Investigators
- Enrico Cecchi, MD, Principal investigator, Maria Vittoria Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03411499
- Sponsor's protocol ID
- Protocol RF-2013-020358691
- Status last verified
- Nov 2023
- First submitted
- 22 Dec 2017
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stroke-free Survival Comparison Between Early Surgery and Conventional Therapy in Left Infective Endocarditis - A Multicenter Partially Randomized Preference Trial (EARLY Study)
- ClinicalTrials.gov ID
- NCT03411499
- Acronym / sponsor ID
- Protocol RF-2013-020358691
- Conditions
- Endocarditis
- Keywords
- Adult, Endocarditis/surgery, Embolism/prevention & control, Cardiovascular Diseases, Costs and Cost Analysis, Quality of life
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study stopped because of low enrollment.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Maria Vittoria HospitalUniversity, hospital or other
- Collaborators
- Ministry of Health, Italy
- Study start
- 22 Dec 2017 (actual)
- Primary completion
- 14 Dec 2020 (actual)
- Study completion
- 14 Dec 2020 (actual)
- First posted
- 26 Jan 2018 (actual)
- 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.
The purpose of the EARLY study is to evaluate the efficacy and effectiveness of early surgery in patients with Infective Endocarditis (IE).
Detailed description
Infective endocarditis (IE) is a relatively rare disease and has a high in-hospital mortality (15-30%) and morbidity due to complications like embolic events, especially in the central nervous system, and heart failure. International guidelines give indications on the optimal timing for surgery, and they strongly recommend early surgery for patients in the active phase of IE with acute cardiac complications (e.g., acute heart failure, uncontrolled infection, and persistent large vegetations after an embolic event). However, at present there is no clear evidence supporting the effectiveness of early surgery or indicating the best time to perform surgery, especially in patients without such conditions. Primary objective of the study is to evaluate whether, in patients with IE and no emergency surgery indication, an early surgical strategy (performed within 72 hours from IE diagnosis) is more effective than conventional therapy in terms of 1-year stroke-free survival. Secondary objectives are: overall survival, risk of embolic, risk of strokes, event-free survival, IE relapse, heart failure, length of hospital stay, hospital re-admission and hospitalization days, strategy compliance, quality of life and health care costs.
This study design consist of a two-arm, open-label, multicenter randomized controlled trial, but patients who decline to be randomized and prefer a certain therapy strategy will be treated according to best practice and included into a prospective observational study after given informed consent. This parallel constructed observational study will be performed with a maximum of consistency to treatment and observation compared to the Randomized clinical trial (RCT). Patients who agree to the randomized trial will be stratified according to centre and clinical features (prosthetic valve,vegetations, valve regurgitation) and randomized with a 1: 1 ratio to 2 different strategies.
According to O'Brien and Fleming group sequential design with a maximum of two stages and a drop-out rate of 10%, a total of 400 randomized patients (200 per group) are required to detect an increase in the stroke-free survival from 82% to 89.5% (corresponding to an Hazard Ratio=0.56) considering a significance level of 5% and a power of 80% and expecting a risk for mortality or stroke at one year with standard treatment equal to 0.18.
EARLY study may help to demonstrate early surgery impact on the contemporary management of the disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Partially Randomized Preference Trial
| Arm | Type | Receives |
|---|---|---|
| Early surgery | Experimental | Procedure: Early surgerySurgery within 72 hours from endocarditis diagnosis |
| Conventional therapy | Active comparator | Procedure: Conventional therapyMedical treatment and a possible delayed surgical intervention according to the current guidelines |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Left-sided Infective Endocarditis (IE) according to modified Duke criteria, fulfilling at least one of the following features:
- Compliance to study treatments
- Euroscore I <20
- Informed consent signature
Key exclusion criteria (11 listed)
- Patients with right-side IE and IE on a cardiac device
- Patients with IE and:
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 |
|---|---|---|
| Early surgerySurgery within 72 hours from endocarditis diagnosis | Procedure or surgery | Early surgery |
| Conventional therapyDelayed surgical intervention or medical treatment according to the current guidelines | Procedure or surgery | Conventional therapy |
Primary outcome
Stroke-free survival
Time frame: 12 months
Time from randomization until the first occurrence of stroke or death. Stroke is defined as a focal neurologic deficit, lasting at least 24 hours and is categorized as ischemic, hemorrhagic or of uncertain type.
16 secondary outcomes
Overall survival
Time frame: 12 months
In-hospital mortality
Time frame: During follow-up, until discharge from hospital, up to 1 year from randomization date
Embolic event during the hospitalization of IE diagnosis
Time frame: During follow-up, until discharge from hospital, up to 1 year from randomization date
Stroke during the hospitalization of IE diagnosis
Time frame: During follow-up, until discharge from hospital, up to 1 year from randomization date
Heart failure during the hospitalization of IE diagnosis
Time frame: During follow-up, until discharge from hospital, up to 1 year from randomization date
Cumulative incidence of stroke
Time frame: 12 months
Cumulative incidence of embolic events
Time frame: 12 months
Cumulative incidence of heart failure
Time frame: 12 months
Cumulative incidence of IE relapse
Time frame: 12 months
Quality of Life using 36-Item Short Form Survey (SF-36)
Time frame: 0, 4, 12 months
Quality of Life using EuroQol five dimension (EQ-5D).
Time frame: 0, 4, 12 months
1-year event-free survival
Time frame: 12 months
Cost-effectiveness
Time frame: 12 months
Length of hospitalization
Time frame: During follow-up, until discharge from hospital, up to 1 year from randomization date
Number of hospital readmission for length .of stay within 1 year for any cause
Time frame: 12 months
Feasibility of early surgery
Time frame: During follow-up, until discharge from hospital, up to 1 year from randomization date
Results and safety
The study was stopped early (reason given: Study stopped because of low enrollment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- A web application to collect data for experimental studiesLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Enrico Cecchi, MD principal investigator
Maria Vittoria Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Early surgery and Conventional therapy in people with Endocarditis, run by Maria Vittoria Hospital 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 9 inclusion and 11 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: stopped early, as of the sponsor's last update on 18 Nov 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.
Are results available for this study?
The study was stopped early (reason given: Study stopped because of low enrollment.). 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?
Stroke-free survival (time frame: 12 months). 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 18 Nov 2023.