Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00638157
Recruitment Status : Terminated (commitment completed)
First Posted : March 18, 2008
Results First Posted : May 22, 2013
Last Update Posted : January 31, 2018
Sponsor:
Information provided by (Responsible Party):
Cubist Pharmaceuticals LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Infective Endocarditis
Interventions Drug: daptomycin
Drug: daptomycin and gentamicin
Enrollment 24
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Daptomycin Daptomycin Plus Gentamicin
Hide Arm/Group Description Intravenous daptomycin 6mg/kg every 24 hours for a recommended minimum duration of 28 days plus a Intravenous daptomycin 6mg/kg every 24 hours for a recommended minimum duration of 28 days plus intravenous gentamicin 1mg/kg every 8 hours for the first 3 days of daptomycin therapy.
Period Title: Overall Study
Started 12 12
Treated 10 12
Completed 5 [1] 8 [1]
Not Completed 7 4
Reason Not Completed
Adverse Event             0             1
Clinical (symptomatic) failure             1             1
Microbiological failure             1             0
Lost to Follow-up             1             0
Physician Decision             1             0
Other             1             2
Randomized, not treated             2             0
[1]
4 subjects completed study drug in this arm
Arm/Group Title Daptomycin Daptomycin Plus Gentamicin Total
Hide Arm/Group Description Intravenous daptomycin 6mg/kg every 24 hours for a recommended minimum duration of 28 days plus a "dummy" infusion of 0.9% normal saline every 8 hours for the first 3 days of daptomycin therapy. Intravenous daptomycin 6mg/kg every 24 hours for a recommended minimum duration of 28 days plus intravenous gentamicin 1mg/kg every 8 hours for the first 3 days of daptomycin therapy. Total of all reporting groups
Overall Number of Baseline Participants 12 12 24
Hide Baseline Analysis Population Description
Intent-to-Treat (ITT) Population used. Includes all randomized subjects.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 12 participants 24 participants
38.9  (10.93) 45.3  (9.90) 42.1  (10.71)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 24 participants
Female
3
  25.0%
5
  41.7%
8
  33.3%
Male
9
  75.0%
7
  58.3%
16
  66.7%
1.Primary Outcome
Title Summary of Clinically Significant Increases in Serum Creatinine by Visit
Hide Description 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.
Time Frame Baseline, EOT Visit, TOC
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population includes all patients who received any dose of study medication.
Arm/Group Title Daptomycin Daptomycin Plus Gentamicin
Hide Arm/Group Description:
Intravenous daptomycin 6mg/kg every 24 hours for a recommended minimum duration of 28 days plus a
Intravenous daptomycin 6mg/kg every 24 hours for a recommended minimum duration of 28 days plus intravenous gentamicin 1mg/kg every 8 hours for the first 3 days of daptomycin therapy.
Overall Number of Participants Analyzed 10 12
Measure Type: Number
Unit of Measure: Participants
Baseline - Any Elevation 0 0
Baseline - No Elevation 10 12
End of Therapy - Any Elevation 0 2
End of Therapy - No Elevation 10 10
Test of Cure - Any Elevation (n=8,9) 0 2
Test of Cure - No Elevation (n=8,9) 8 7
2.Secondary Outcome
Title Summary of the Investigator's Assessment of Clinical Response at the TOC Visit
Hide Description TOC/Safety visit occurred 21 to 28 days after the last dose of daptomycin therapy. Clinical response was assessed by the investigator as cure, improvement, failure, and unable to evaluate. Microbiological response, which was determined by the sponsor based on review of baseline and post-baseline culture results, included success, failure, and nonevaluable. TC=Treatment Cure; TF=Treatment Failure; TI=Treatment Improved.
Time Frame TOC Visit
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat (mITT) population includes all ITT patients who received at least one dose of study medication.
Arm/Group Title Daptomycin Daptomycin Plus Gentamicin
Hide Arm/Group Description:
Intravenous daptomycin 6mg/kg every 24 hours for a recommended minimum duration of 28 days plus a "dummy" infusion of 0.9% normal saline every 8 hours for the first 3 days of daptomycin therapy.
Intravenous daptomycin 6mg/kg every 24 hours for a recommended minimum duration of 28 days plus intravenous gentamicin 1mg/kg every 8 hours for the first 3 days of daptomycin therapy.
Overall Number of Participants Analyzed 9 11
Measure Type: Number
Unit of Measure: Participants
TC (clinical cure, microbiological success) 4 5
TC (clinical cure, microbiological nonevaluable) 0 0
TF (clinical failure, microbiological success) 1 1
TF (clinical cure, microbiological failure) 0 0
TF (clinical failure, microbiological failure) 2 0
TF (clinical improved, microbiological failure) 0 0
TF (clinical failure, microbiological nonevaluable 0 2
TI (clinical improved, microbiological success) 0 1
TI (clin improved, microbiological nonevaluable) 0 0
Non-evaluable 2 2
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Daptomycin Daptomycin Plus Gentamicin
Hide Arm/Group Description Intravenous daptomycin 6mg/kg every 24 hours for a recommended minimum duration of 28 days plus a "dummy" infusion of 0.9% normal saline every 8 hours for the first 3 days of daptomycin therapy. Intravenous daptomycin 6mg/kg every 24 hours for a recommended minimum duration of 28 days plus intravenous gentamicin 1mg/kg every 8 hours for the first 3 days of daptomycin therapy.
All-Cause Mortality
Daptomycin Daptomycin Plus Gentamicin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Daptomycin Daptomycin Plus Gentamicin
Affected / at Risk (%) Affected / at Risk (%)
Total   2/10 (20.00%)   5/12 (41.67%) 
Cardiac disorders     
Tachycardia  0/10 (0.00%)  1/12 (8.33%) 
Gastrointestinal disorders     
Gastrointestinal haemorrhage  0/10 (0.00%)  1/12 (8.33%) 
Infections and infestations     
Arthritis bacterial  0/10 (0.00%)  1/12 (8.33%) 
Bacteraemia  1/10 (10.00%)  0/12 (0.00%) 
Endocarditis  1/10 (10.00%)  0/12 (0.00%) 
Osteomyelitis  0/10 (0.00%)  1/12 (8.33%) 
Septic shock  0/10 (0.00%)  1/12 (8.33%) 
Renal and urinary disorders     
Renal failure  0/10 (0.00%)  1/12 (8.33%) 
Respiratory, thoracic and mediastinal disorders     
Haemoptysis  0/10 (0.00%)  1/12 (8.33%) 
Skin and subcutaneous tissue disorders     
Rash  0/10 (0.00%)  1/12 (8.33%) 
Vascular disorders     
Hypertension  0/10 (0.00%)  1/12 (8.33%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Daptomycin Daptomycin Plus Gentamicin
Affected / at Risk (%) Affected / at Risk (%)
Total   8/10 (80.00%)   11/12 (91.67%) 
Blood and lymphatic system disorders     
Anaemia  2/10 (20.00%)  1/12 (8.33%) 
Splenomegaly  0/10 (0.00%)  1/12 (8.33%) 
Ear and labyrinth disorders     
Hypoacusis  1/10 (10.00%)  0/12 (0.00%) 
Eye disorders     
Abnormal sensation in eye  1/10 (10.00%)  0/12 (0.00%) 
Eye pain  1/10 (10.00%)  0/12 (0.00%) 
Vision blurred  1/10 (10.00%)  0/12 (0.00%) 
Gastrointestinal disorders     
Constipation  4/10 (40.00%)  3/12 (25.00%) 
Diarrhoea  0/10 (0.00%)  2/12 (16.67%) 
Nausea  1/10 (10.00%)  2/12 (16.67%) 
Umbilical hernia  1/10 (10.00%)  0/12 (0.00%) 
Vomiting  1/10 (10.00%)  1/12 (8.33%) 
General disorders     
Catheter related complication  3/10 (30.00%)  1/12 (8.33%) 
Chest discomfort  1/10 (10.00%)  0/12 (0.00%) 
Chills  1/10 (10.00%)  0/12 (0.00%) 
Influenza like illness  0/10 (0.00%)  1/12 (8.33%) 
Malaise  1/10 (10.00%)  0/12 (0.00%) 
Non-cardiac chest pain  0/10 (0.00%)  1/12 (8.33%) 
Oedema peripheral  2/10 (20.00%)  0/12 (0.00%) 
Pyrexia  2/10 (20.00%)  0/12 (0.00%) 
Infections and infestations     
Bacterial sepsis  0/10 (0.00%)  1/12 (8.33%) 
Escherichia urinary tract infection  0/10 (0.00%)  1/12 (8.33%) 
Fungal skin infection  1/10 (10.00%)  0/12 (0.00%) 
Hepatitis C  0/10 (0.00%)  1/12 (8.33%) 
Osteomyelitis  0/10 (0.00%)  1/12 (8.33%) 
Paronychia  1/10 (10.00%)  0/12 (0.00%) 
Injury, poisoning and procedural complications     
Contusion  1/10 (10.00%)  0/12 (0.00%) 
Procedural pain  1/10 (10.00%)  0/12 (0.00%) 
Wound  1/10 (10.00%)  0/12 (0.00%) 
Investigations     
Aspartate aminotransferase increased  1/10 (10.00%)  0/12 (0.00%) 
Blood creatine phosphokinase increased  0/10 (0.00%)  1/12 (8.33%) 
Blood creatinine increased  1/10 (10.00%)  0/12 (0.00%) 
Blood glucose increased  0/10 (0.00%)  1/12 (8.33%) 
Cardiac murmur  0/10 (0.00%)  1/12 (8.33%) 
Haematocrit decreased  1/10 (10.00%)  0/12 (0.00%) 
Haemoglobin decreased  1/10 (10.00%)  0/12 (0.00%) 
Hepatic enzyme increased  1/10 (10.00%)  0/12 (0.00%) 
Red blood cell count decreased  1/10 (10.00%)  0/12 (0.00%) 
White blood cell count increased  1/10 (10.00%)  0/12 (0.00%) 
Metabolism and nutrition disorders     
Diabetes mellitus inadequate control  0/10 (0.00%)  1/12 (8.33%) 
Hyperkalaemia  1/10 (10.00%)  2/12 (16.67%) 
Hyperphosphataemia  1/10 (10.00%)  0/12 (0.00%) 
Hypokalaemia  1/10 (10.00%)  0/12 (0.00%) 
Hypomagnesaemia  2/10 (20.00%)  2/12 (16.67%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms  1/10 (10.00%)  0/12 (0.00%) 
Musculoskeletal pain  1/10 (10.00%)  0/12 (0.00%) 
Neck pain  1/10 (10.00%)  0/12 (0.00%) 
Pain in extremity  1/10 (10.00%)  0/12 (0.00%) 
Nervous system disorders     
Dysgeusia  1/10 (10.00%)  0/12 (0.00%) 
Headache  2/10 (20.00%)  0/12 (0.00%) 
Somnolence  1/10 (10.00%)  0/12 (0.00%) 
Psychiatric disorders     
Agitation  0/10 (0.00%)  1/12 (8.33%) 
Anxiety  4/10 (40.00%)  1/12 (8.33%) 
Insomnia  1/10 (10.00%)  1/12 (8.33%) 
Renal and urinary disorders     
Renal impairment  0/10 (0.00%)  1/12 (8.33%) 
Urinary incontinence  0/10 (0.00%)  1/12 (8.33%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1/10 (10.00%)  0/12 (0.00%) 
Nasal congestion  2/10 (20.00%)  0/12 (0.00%) 
Skin and subcutaneous tissue disorders     
Dry skin  0/10 (0.00%)  1/12 (8.33%) 
Skin lesion  0/10 (0.00%)  1/12 (8.33%) 
Skin ulcer  1/10 (10.00%)  0/12 (0.00%) 
Vascular disorders     
Hypertension  1/10 (10.00%)  1/12 (8.33%) 
Hypotension  1/10 (10.00%)  1/12 (8.33%) 
Phlebitis  1/10 (10.00%)  0/12 (0.00%) 
As the study was terminated prematurely, conclusions that can be drawn from the efficacy results are limited.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The first publication is initiated by Cubist. If First Publication not published within 1 year of Study conclusion or termination, Investigator has right to publish and disclose the Data. Prior to any submission for publication, presentation, or communication of results or information arising from the Study, Investigator shall provide Cubist at least 90 days for review and comment upon the manuscript or other material for such publication or presentation.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Ed Campanaro / Vice President, Clinical Operations
Organization: Cubist Pharmaceuticals
Phone: 781-860-8318
EMail: ed.campanaro@cubist.com
Layout table for additonal information
Responsible Party: Cubist Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT00638157    
Other Study ID Numbers: 3009-010
DAP-4IE-06-03 ( Other Identifier: Cubist Study Number )
First Submitted: March 12, 2008
First Posted: March 18, 2008
Results First Submitted: March 4, 2013
Results First Posted: May 22, 2013
Last Update Posted: January 31, 2018