Phase 4 Efficacy and Safety Study of Cubicin® With and Without Combination Therapy in S. Aureus Infective Endocarditis (SAIE)
Condition: Infective Endocarditis
MeSH terms: Endocarditis, Bacterial; Endocarditis
Intervention: daptomycin; daptomycin and gentamicin
Intervention description: Intravenous (i.v.) 6 mg/kg q24h; i.v. daptomycin 6 mg/kg q24h plus initial i.v. gentamicin
Intervention MeSH terms: Gentamicins; Daptomycin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gram-positive bacterial infections; Staph Aureus; endocarditis; bacteremia; methicillin-resistant Staphylococcus aureus (MRSA)

Summary:

      multicenter, randomized, double blind study to describe the safety and efficacy of daptomycin
      (6 mg/kg q24h) with and without concomitant initial gentamicin combination therapy in the
      treatment of SAIE
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written informed consent has been obtained;

          2. Male or female ≥18 years of age;

          3. IVDU (as confirmed by history of drug abuse within the past 3 months or recent needle
             track marks);

          4. Definite or possible IE according to the modified Duke Criteria (see Appendix A); [17
             ];

          5. Two blood cultures positive for S. aureus obtained within 96 hours prior to first dose
             of study medication acquired by fresh venipuncture using aseptic technique and
             analyzed at the local laboratory (see Appendix B).

        Exclusion Criteria:

          1. Intravascular foreign material in place at the time that the positive blood culture
             was drawn (e.g., intracardiac pacemaker wires, percutaneous or implanted venous
             catheters, vascular grafts), (exception: vascular stents that have been in place for
             >6 months or permanent pacemaker wires attached via epicardial leads are allowed);

          2. High likelihood of LIE as indicated by:

               1. Prior diagnosis of predisposing left-sided valvular pathology (e.g., rheumatic
                  heart disease, bicuspid aortic valve); or

               2. Findings on screening examination of left-sided valvular pathology (e.g.,
                  diastolic murmur of aortic insufficiency); or

               3. Findings on screening examination of major systemic emboli to visceral organs
                  (e.g. cerebral or splenic infarct). Patients may be included if their only
                  findings are consistent with microvascular phenomena due to immune complexes
                  (e.g., splinter hemorrhages, conjunctival petechiae, Roth's spots, Osler's nodes,
                  Janeway's lesions, microhematuria).

             Note: Any patient enrolled in the study that is subsequently found to have LIE may be
             continued in the trial if determined to be clinically improving by the Investigator.

          3. Prosthetic heart valve;

          4. Baseline Creatinine clearance of <30 mL/min (as calculated by the Cockcroft-Gault
             equation using actual body weight);

          5. Baseline CPK value 5 X upper limit of normal (ULN) in conjunction with symptoms of
             myalgia or baseline CPK value 10 X ULN without symptoms;

          6. Alanine aminotransferase (ALT) >5 X ULN;

          7. Aspartate aminotransferase (AST) >5 X ULN;

          8. Moribund clinical condition (i.e. high likelihood of death within 3 days after
             randomization);

          9. Shock or hypotension (supine systolic blood pressure <80 mm Hg) or oliguria (urine
             output <20 mL/h) unresponsive to fluids or pressors within 4 hours;

         10. Known pneumonia or osteomyelitis;

         11. Polymicrobial infection or bacteremia due to a pathogen other than S. aureus;

         12. Neutropenia (absolute neutrophil count < 0.5 X 103/μL) and/or lymphopenia (CD4
             lymphocytes <0.2X 103/μL);

         13. Anticipated to require non-study antibiotics that may be potentially effective against
             S. aureus;

         14. Prior gentamicin therapy > 1 day;

         15. Documented history of significant allergy or intolerance to any of the study
             medications;

         16. Unlikely to comply with study procedures;

         17. Pregnant or nursing. All females with childbearing potential will have a pregnancy
             test performed at the local laboratory.

         18. Female of childbearing potential and not willing to practice barrier methods of birth
             control (e.g., condoms or diaphragms together with spermicidal foam or gel) during
             treatment and for at least 28 days after treatment with study medication