A Phase 4 Multicenter, Randomized, Double Blind Study to Describe the Efficacy and Safety of Cubicin® (Daptomycin for Injection) With and Without Initial Gentamicin Combination Therapy in the Treatment of S. Aureus Infective Endocarditis
Overview
- Phase
- Phase 4
- Intervention
- daptomycin
- Conditions
- Infective Endocarditis
- Sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Enrollment
- 24
- Locations
- 4
- Primary Endpoint
- Summary of Clinically Significant Increases in Serum Creatinine by Visit
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief 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
Detailed Description
Patients will be randomized to either of the following two treatment arms: * Arm 1: daptomycin * Arm 2: daptomycin with initial i.v. gentamicin Patients who meet all the inclusion criteria and exhibit none of the exclusion criteria may be enrolled. Intravenous drug user (IVDU) patients may be randomized and study drug begun on the basis of two separate peripheral blood cultures positive for S. aureus obtained within 96 hours prior to the first dose of study drug. The recommended minimum duration of treatment for daptomycin will be 28 days. The duration of treatment for gentamicin will be 3 days. During study treatment, regular assessments (including weekly safety laboratory testing including CPK) will be performed. An End-of-Therapy (EOT) evaluation will be performed on the day of or 1-2 days after completion of daptomycin study drug or upon early termination (ET). All patients will have a post-therapy visit for Test of Cure (TOC)/Safety performed 21-28 days following the last dose of daptomycin study drug.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent has been obtained;
- •Male or female ≥18 years of age;
- •IVDU (as confirmed by history of drug abuse within the past 3 months or recent needle track marks);
- •Definite or possible IE according to the modified Duke Criteria (see Appendix A); \[17 \];
- •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
- •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);
- •High likelihood of LIE as indicated by:
- •Prior diagnosis of predisposing left-sided valvular pathology (e.g., rheumatic heart disease, bicuspid aortic valve); or
- •Findings on screening examination of left-sided valvular pathology (e.g., diastolic murmur of aortic insufficiency); or
- •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.
- •Prosthetic heart valve;
- •Baseline Creatinine clearance of \<30 mL/min (as calculated by the Cockcroft-Gault equation using actual body weight);
- •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;
- •Alanine aminotransferase (ALT) \>5 X ULN;
Arms & Interventions
Daptomycin Alone
daptomycin 6 mg/kg q24h for treatment of right-sided infective endocarditis
Intervention: daptomycin
Daptomycin plus gentamicin
daptomycin 6 mg/kg q24h with concomitant initial gentamicin dosed for the first 2 days of therapy for the treatment of right-sided infective endocarditis
Intervention: daptomycin and gentamicin
Outcomes
Primary Outcomes
Summary of Clinically Significant Increases in Serum Creatinine by Visit
Time Frame: Baseline, EOT Visit, TOC
The End of Treatment (EOT)/Early Termination (ET) visit occurred on the day that therapy was stopped or up to 2 days after the last dose of daptomycin. The Test of Cure (TOC)/Safety visit occurred 21 to 28 days after the last dose of daptomycin therapy. The overall median duration of treatment was 13.0 days in both the daptomycin group and the combination therapy group. The definition of elevated serum creatinine at baseline is \>3.0 mg/dL, and not elevated is ≤3.0 mg/dL. Clinically significant increases in serum creatinine is defined as an increase ≥0.5 mg/dL for patients with a baseline value ≤3.0 mg/dL or ≥1.0 mg/dL for patients with a baseline value \>3.0 mg/dL.
Secondary Outcomes
- Summary of the Investigator's Assessment of Clinical Response at the TOC Visit(TOC Visit)