SATIE: Short-course Antibiotic Treatment in Gram-positive Cocci Infective Endocarditis

Sponsor

Carmen Olmos Blanco (Other)

Overall Status

Recruiting

CT.gov ID

NCT04222257

Collaborator

(none)

298

Enrollment

Location

Arms

32.1

Anticipated Duration (Months)

9.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background: it is well known that most serious complications of infective endocarditis (IE) appear in the so-called "critical phase" of the disease, which are the first days after diagnosis. Subsequently, the vast majority of patients who overcome this acute phase has a favourable evolution, and usually stay in the hospital for a long time only to complete antibiotic therapy.

In stable patients with adequate response to antibiotic treatment, without signs of persistent infection or metastatic foci such as spondylodiscitis, it is likely that a shorter antibiotic regimen would be an efficient and safe alternative, as has already been confirmed in patients with IE on tricuspid valves caused by a microorganism considered virulent such as

aureus. This attractive alternative would improve patients' quality of life, save costs, and decrease the risk of complications related to the adverse effects of prolonged antibiotic treatment.

Objectives: to compare the incidence of the composite endpoint of all-cause mortality, unplanned cardiac surgery, symptomatic embolisms and relapses within 6 months after the inclusion between patients with IE caused by gram-positive cocci receiving a short-course of 2 weeks of antibiotic therapy and those patients receiving conventional antibiotic therapy (4-6 weeks).

Methodology: multicenter, prospective, randomized, controlled open-label, phase IV clinical trial. Sample: patients with IE caused by gram-positive cocci, having received at least 10 days of conventional antibiotic treatment, and at least 7 days after surgery when indicated, without clinical, analytical, microbiological or echocardiographic signs of persistent infection. Estimated sample size: 298 patients. Intervention: Control group: standard antibiotic therapy, according to ESC guidelines recommendations, for 4 to 6 weeks. Experimental group: short-course antibiotic therapy for 2 weeks. The prevalence of previously known risk factors for adverse events will be compared between the two groups to confirm that randomization have worked properly. The incidence of the composite endpoint of all-cause mortality, unplanned cardiac surgery, symptomatic embolisms and relapses within 6 months after the inclusion in the study will be prospectively registered and compared.

Condition or Disease	Intervention/Treatment	Phase
Endocarditis, Bacterial	Drug: Antibiotics Drug: Antibiotics	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

298 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Short-course Antibiotic Regimen Compared to Conventional Antibiotic Treatment for Gram-positive Cocci Infective Endocarditis: Randomized Clinical Trial

Actual Study Start Date :

Jan 26, 2021

Anticipated Primary Completion Date :

Mar 31, 2023

Anticipated Study Completion Date :

Sep 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Short course Patients allocated to this group will receive a short course of antibiotic therapy for 2 weeks.	Drug: Antibiotics Patients allocated to this group will receive a short course of antibiotic therapy for 2 weeks.
Active Comparator: Standard course Those patients allocated to continue with standard parenteral treatment will maintain the same antibiotic treatment for 4 to 6 weeks.	Drug: Antibiotics Patients allocated to continue with standard parenteral treatment will maintain the same antibiotic treatment for 4 to 6 weeks.

Arm

Intervention/Treatment

Experimental: Short course

Patients allocated to this group will receive a short course of antibiotic therapy for 2 weeks.

Drug: Antibiotics

Patients allocated to this group will receive a short course of antibiotic therapy for 2 weeks.

Active Comparator: Standard course

Those patients allocated to continue with standard parenteral treatment will maintain the same antibiotic treatment for 4 to 6 weeks.

Drug: Antibiotics

Patients allocated to continue with standard parenteral treatment will maintain the same antibiotic treatment for 4 to 6 weeks.

Outcome Measures

Primary Outcome Measures

Composite endopoint [6 months]
To compare the incidence of the composite endpoint that includes all-cause mortality, unplanned cardiac surgery, symptomatic embolisms and relapses within 6 months after the inclusion, between patients with IE caused by gram-positive cocci receiving a short course of 2 weeks of antibiotic therapy and those patients receiving conventional antibiotic therapy for 4-6 weeks.

Secondary Outcome Measures

Perceived quality of life: SF-12 [4 weeks]
Determination of quality of life (SF-12)
Functional performance [4 weeks]
Determination of functional performance according to the short performance physical battery test (SPPB)
Clinical complications [6 months]
Clinical complications related to hospital stay (nosocomial infections, intravascular catheter-related infections)
Total hospital length of stay [6 months]
Total hospital length of stay in the next 6 months after the inclusion in the study

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Definite IE, according to modified ESC 2015 criteria, caused by gram-positive cocci (staphylococci, streptococci and enterococci), including native, prosthetic valve IE and cardiac device-related IE.
18 years old or older.
Patients treated for at least 10 days of appropriate parenteral antibiotic therapy overall (according to guidelines and microbiology sensitivity testing), and at least 7 days of parenteral antibiotic therapy after valve surgery when indicated.
Absence of fever, microbiological or analytical findings suggesting persistent infection at randomization.
Absence of locally uncontrolled infection signs (abscess, pseudoaneurysm, fistula, enlarging vegetation) at randomization, confirmed by recent transesophageal echocardiography (performed within 48 h of randomization).
Women of childbearing potential who will agree to the use of effective contraceptive methods while on antibiotic treatment.

Exclusion Criteria:

Patients who have received appropriate parenteral antibiotic therapy for infective endocarditis for more than 12 days.
Patients not suitable to be discharged after 10 days of conventional treatment, due to clinical reasons (sequels of stroke that prevent discharge, progressive renal failure, hepatic failure).
Patients receiving chemotherapy or immunosuppressive therapy.
Pregnant or breastfeeding women.
Need of prolonged antibiotic therapy due to spondylodiscitis or other septic complication.
Absence of patient's ability or commitment to continue follow-up after being discharged from hospital.
Inability to give informed consent to participation.
Cognitive impairment or lack of language skills needed to complete the questionnaires.
Patients who meet urgent cardiac surgery ESC criteria but are considered inoperable due to high surgical risk.