Phase 4 Efficacy and Safety Study of Cubicin® With and Without Combination Therapy in S. Aureus Infective Endocarditis (SAIE)

NCT00638157 | Terminated Phase 4 Results

• 2 other identifiers: 3009-010DAP-4IE-06-03
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 4

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

Conditions

Infective Endocarditis

Keywords

Gram-positive bacterial infections; Staph Aureus; endocarditis; bacteremia; methicillin-resistant Staphylococcus aureus (MRSA)

Outcome Measures

Primary Outcomes (1)

• Summary of Clinically Significant Increases in Serum Creatinine by Visit

  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.

  Baseline, EOT Visit, TOC

Secondary Outcomes (1)

• Summary of the Investigator's Assessment of Clinical Response at the TOC Visit

  TOC Visit

Study Arms (2)

Daptomycin Alone

ACTIVE COMPARATOR

daptomycin 6 mg/kg q24h for treatment of right-sided infective endocarditis

Drug: daptomycin

Daptomycin plus gentamicin

EXPERIMENTAL

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

Drug: daptomycin and gentamicin

Interventions

daptomycin DRUG

Intravenous (i.v.) 6 mg/kg q24h

Also known as: Cubicin, daptomycin for injection

Daptomycin Alone

daptomycin and gentamicin DRUG

i.v. daptomycin 6 mg/kg q24h plus initial i.v. gentamicin

Also known as: Cubicin, daptomycin for injection, gentamicin

Daptomycin plus gentamicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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;
• Aspartate aminotransferase (AST) \>5 X ULN;
• Moribund clinical condition (i.e. high likelihood of death within 3 days after randomization);
• 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;
• Known pneumonia or osteomyelitis;
• Polymicrobial infection or bacteremia due to a pathogen other than S. aureus;

Sponsors & Collaborators

• Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (4)

Denver Health Medical Center

Denver, Colorado, 80204, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Temple University School of Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

MeSH Terms

Conditions

Endocarditis; Gram-Positive Bacterial Infections; Staphylococcal Infections; Bacteremia

Interventions

Daptomycin; Injections; Gentamicins

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins; Drug Administration Routes; Drug Therapy; Therapeutics; Aminoglycosides; Glycosides; Carbohydrates

Limitations and Caveats

As the study was terminated prematurely, conclusions that can be drawn from the efficacy results are limited.

Results Point of Contact

• Title: Ed Campanaro / Vice President, Clinical Operations
• Organization: Cubist Pharmaceuticals

ed.campanaro@cubist.com

781-860-8318

Study Officials

• Paula Bokesch, M.D.

  Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2008
• First Posted: March 18, 2008
• Study Start: February 13, 2009
• Primary Completion: November 9, 2011
• Study Completion: November 9, 2011
• Last Updated: February 2, 2021
• Results First Posted: May 22, 2013

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share

Locations

US (4)