Daptomycin as an Adjuvant Agent in the Treatment of Enterococcal Native Valve Endocarditis.

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00401960
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arms: 2
• Duration (Months): 25
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The aim of this study is to determine the safety and efficacy of daptomycin when used as an adjuvant agent to standard care in the treatment of proven native valve Enterococcal endocarditis. Patients with this disease will be offered the option of receiving daptomycin at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already receiving. The hypothesis of this study is that daptomycin added to standard therapy for Enterococcal endocarditis is safe and efficacious.

Patients who receive daptomycin + standard therapy will be compared to patients who receive standard therapy alone with respect to the following outcomes:

1. Safety.

2. The frequency of any Grade 3 or 4 toxicity (DAIDS scale) will be measured.

3. The frequency of muscle toxicity or renal toxicity, as determined by predefined criteria.

4. Efficacy.

5. Clinical efficacy.

• Time to clearance of bacteremia

• Cure at 6 weeks following completion of antibiotic therapy

• Mortality at 6 weeks following completion of antibiotic therapy

1. Microbiologic efficacy.

• Peak and trough serum bactericidal titers

• The minimum bactericidal concentration of Enterococci to daptomycin

We expect to enroll 40 patients over 2 years.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open Label Study to Assess the Efficacy and Safety of Daptomycin in Combination With Anti-Cell Wall Active Therapy in the Treatment of Enterococcal Endocarditis
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Daptomycin adjunctive group Patients with enterococcal endocarditis who elect to receive daptomycin at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already receiving	Drug: Daptomycin; daptomycin at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already receiving for native valve enterococcal endocarditis; Other Names: Cubicin
No Intervention: standard of care Patients with enterococcal endocarditis who elect to receive standard of care therapy as prescribed by their primary physician

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Any Grade 3 or 4 Toxicity (DAIDS Scale) [weekly]

   Number of Participants any Grade 3 or 4 toxicity (DAIDS scale); please see adverse event table for details

2. Number of Participants With Muscle Toxicity or Renal Toxicity, as Determined by Predefined Criteria [weekly]

   Number of Participants with creatine kinase elevation > 3x upper limit of normal or elevations of serum Cr >= 30% above baseline

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18 or over

• Definite Enterococcal endocarditis, as defined by modified Duke criteria

• Able to complete follow-up 3 and 6 weeks following completion of intravenous antibiotic therapy

Exclusion Criteria:

• Pregnancy or breast feeding

• Creatine phosphokinase levels over two times the upper limit of normal

• Renal insufficiency or dialysis requirement.

• Presence of chronic indwelling bloodstream catheters or foreign body devices suspected as primary or secondary sites of enterococcal infection unamenable to removal or replacement

• Inability to discontinue or abstain from use of a HMG CoA reductase inhibitor during the study period.

• Hypersensitivity to any of the study medications.

• Any condition that, in the investigator's opinion, may interfere with protocol compliance including, but not limited to, active substance abuse and/or dementia.

• Prosthetic valve endocarditis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NewYork-Presbyterian Hospital, Weill Cornell Campus	New York	New York	United States	10021

Sponsors and Collaborators

• Weill Medical College of Cornell University

Investigators

• Principal Investigator: Kyu Y Rhee, MD, PhD, Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Rhee, Kyu Y., Assistant Professor, Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT00401960
• Other Study ID Numbers: 0507008023
• First Posted: Nov 22, 2006
• Last Update Posted: May 3, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Rhee, Kyu Y., Assistant Professor, Weill Medical College of Cornell University: Enterococcus; Daptomycin; Endocarditis
• Additional relevant MeSH terms: Endocarditis, Bacterial; Endocarditis; Daptomycin

Study Results

Participant Flow

Arm/Group Title	Adjunctive Daptomycin Group	Standard of Care Group
Arm/Group Description	please see study description for study enrollment	as per study description
Period Title: Overall Study
STARTED	5	1
COMPLETED	0	1
NOT COMPLETED	5	0

Baseline Characteristics

Arm/Group Title	Adjunctive Daptomycin Group	Standard of Care Group	Total
Arm/Group Description	please see study description for study enrollment	as per study description	Total of all reporting groups
Overall Participants	5	1	6
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 60%	0 0%	3 50%
>=65 years	2 40%	1 100%	3 50%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	69	74	70
Sex: Female, Male (Count of Participants)
Female	1 20%	0 0%	1 16.7%
Male	4 80%	1 100%	5 83.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Any Grade 3 or 4 Toxicity (DAIDS Scale)
Description	Number of Participants any Grade 3 or 4 toxicity (DAIDS scale); please see adverse event table for details
Time Frame	weekly

Outcome Measure Data

Analysis Population Description

Study terminated due to insufficient enrollment; therefore data not sufficient for planned analysis

Arm/Group Title	Adjunctive Daptomycin Group	Standard of Care Group
Arm/Group Description	please see study description for study enrollment	as per study description
Measure Participants	5	1
Count of Participants [Participants]	4 80%	0 0%

2. Primary Outcome

Title	Number of Participants With Muscle Toxicity or Renal Toxicity, as Determined by Predefined Criteria
Description	Number of Participants with creatine kinase elevation > 3x upper limit of normal or elevations of serum Cr >= 30% above baseline
Time Frame	weekly

Outcome Measure Data

Analysis Population Description

study terminated due to inadequate enrollment; therefore data not sufficient for planned analysis

Arm/Group Title	Daptomycin Adjunctive Group	Standard of Care
Arm/Group Description	Patients with enterococcal endocarditis who elect to receive daptomycin at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already receiving Daptomycin: daptomycin at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already receiving for native valve enterococcal endocarditis	Patients with enterococcal endocarditis who elect to receive standard of care therapy as prescribed by their primary physician
Measure Participants	5	1
Elevated serum creatinine >= 30% above baseline	1 20%	1 100%
Elevate serum creatine kinase > 3X ULN	0 0%	0 0%

Adverse Events

Time Frame	2 years; however, study terminated due to lack of eligible study participants
Arm/Group Title	Adjunctive Daptomycin Group		Standard of Care Group
Arm/Group Description	please see study description for study enrollment		as per study description
All Cause Mortality
	Adjunctive Daptomycin Group		Standard of Care Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Adjunctive Daptomycin Group		Standard of Care Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		0/1 (0%)
Blood and lymphatic system disorders
death	1/5 (20%)	1	0/1 (0%)	0
Cardiac disorders
hemopericardium	2/5 (40%)	2	0/1 (0%)	0
Infections and infestations
death	1/5 (20%)	1	0/1 (0%)	0
Renal and urinary disorders
Cr elevation	1/5 (20%)	1	0/1 (0%)	0
Other (Not Including Serious) Adverse Events
	Adjunctive Daptomycin Group		Standard of Care Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/1 (0%)

Limitations/Caveats

study terminated due to insufficient enrollment; data therefore not analyzed

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.