Trial Outcomes & Findings for Phase 4 Efficacy and Safety Study of Cubicin® With and Without Combination Therapy in S. Aureus Infective Endocarditis (SAIE) (NCT NCT00638157)
NCT ID: NCT00638157
Last Updated: 2021-02-02
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
24 participants
Primary outcome timeframe
Baseline, EOT Visit, TOC
Results posted on
2021-02-02
Participant Flow
Participant milestones
| Measure |
Daptomycin
Intravenous daptomycin 6mg/kg every 24 hours for a recommended minimum duration of 28 days plus a
|
Daptomycin Plus Gentamicin
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 Study
STARTED
|
12
|
12
|
|
Overall Study
Treated
|
10
|
12
|
|
Overall Study
COMPLETED
|
5
|
8
|
|
Overall Study
NOT COMPLETED
|
7
|
4
|
Reasons for withdrawal
| Measure |
Daptomycin
Intravenous daptomycin 6mg/kg every 24 hours for a recommended minimum duration of 28 days plus a
|
Daptomycin Plus Gentamicin
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 Study
Adverse Event
|
0
|
1
|
|
Overall Study
Clinical (symptomatic) failure
|
1
|
1
|
|
Overall Study
Microbiological failure
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Other
|
1
|
2
|
|
Overall Study
Randomized, not treated
|
2
|
0
|
Baseline Characteristics
Phase 4 Efficacy and Safety Study of Cubicin® With and Without Combination Therapy in S. Aureus Infective Endocarditis (SAIE)
Baseline characteristics by cohort
| Measure |
Daptomycin
n=12 Participants
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.
|
Daptomycin Plus Gentamicin
n=12 Participants
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
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.9 years
STANDARD_DEVIATION 10.93 • n=5 Participants
|
45.3 years
STANDARD_DEVIATION 9.90 • n=7 Participants
|
42.1 years
STANDARD_DEVIATION 10.71 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, EOT Visit, TOCPopulation: Safety Population includes all patients who received any dose of study medication.
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.
Outcome measures
| Measure |
Daptomycin
n=10 Participants
Intravenous daptomycin 6mg/kg every 24 hours for a recommended minimum duration of 28 days plus a
|
Daptomycin Plus Gentamicin
n=12 Participants
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.
|
|---|---|---|
|
Summary of Clinically Significant Increases in Serum Creatinine by Visit
Baseline - Any Elevation
|
0 Participants
|
0 Participants
|
|
Summary of Clinically Significant Increases in Serum Creatinine by Visit
Baseline - No Elevation
|
10 Participants
|
12 Participants
|
|
Summary of Clinically Significant Increases in Serum Creatinine by Visit
End of Therapy - Any Elevation
|
0 Participants
|
2 Participants
|
|
Summary of Clinically Significant Increases in Serum Creatinine by Visit
End of Therapy - No Elevation
|
10 Participants
|
10 Participants
|
|
Summary of Clinically Significant Increases in Serum Creatinine by Visit
Test of Cure - Any Elevation (n=8,9)
|
0 Participants
|
2 Participants
|
|
Summary of Clinically Significant Increases in Serum Creatinine by Visit
Test of Cure - No Elevation (n=8,9)
|
8 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: TOC VisitPopulation: Modified Intent-to-Treat (mITT) population includes all ITT patients who received at least one dose of study medication.
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.
Outcome measures
| Measure |
Daptomycin
n=9 Participants
Intravenous daptomycin 6mg/kg every 24 hours for a recommended minimum duration of 28 days plus a
|
Daptomycin Plus Gentamicin
n=11 Participants
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.
|
|---|---|---|
|
Summary of the Investigator's Assessment of Clinical Response at the TOC Visit
TC (clinical cure, microbiological success)
|
4 Participants
|
5 Participants
|
|
Summary of the Investigator's Assessment of Clinical Response at the TOC Visit
TC (clinical cure, microbiological nonevaluable)
|
0 Participants
|
0 Participants
|
|
Summary of the Investigator's Assessment of Clinical Response at the TOC Visit
TF (clinical failure, microbiological success)
|
1 Participants
|
1 Participants
|
|
Summary of the Investigator's Assessment of Clinical Response at the TOC Visit
TF (clinical cure, microbiological failure)
|
0 Participants
|
0 Participants
|
|
Summary of the Investigator's Assessment of Clinical Response at the TOC Visit
TF (clinical failure, microbiological failure)
|
2 Participants
|
0 Participants
|
|
Summary of the Investigator's Assessment of Clinical Response at the TOC Visit
TF (clinical improved, microbiological failure)
|
0 Participants
|
0 Participants
|
|
Summary of the Investigator's Assessment of Clinical Response at the TOC Visit
TF (clinical failure, microbiological nonevaluable
|
0 Participants
|
2 Participants
|
|
Summary of the Investigator's Assessment of Clinical Response at the TOC Visit
TI (clinical improved, microbiological success)
|
0 Participants
|
1 Participants
|
|
Summary of the Investigator's Assessment of Clinical Response at the TOC Visit
TI (clin improved, microbiological nonevaluable)
|
0 Participants
|
0 Participants
|
|
Summary of the Investigator's Assessment of Clinical Response at the TOC Visit
Non-evaluable
|
2 Participants
|
2 Participants
|
Adverse Events
Daptomycin
Serious events: 2 serious events
Other events: 8 other events
Deaths: 0 deaths
Daptomycin Plus Gentamicin
Serious events: 5 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Daptomycin
n=10 participants at risk
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.
|
Daptomycin Plus Gentamicin
n=12 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
Tachycardia
|
0.00%
0/10
|
8.3%
1/12
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/10
|
8.3%
1/12
|
|
Infections and infestations
Arthritis bacterial
|
0.00%
0/10
|
8.3%
1/12
|
|
Infections and infestations
Bacteraemia
|
10.0%
1/10
|
0.00%
0/12
|
|
Infections and infestations
Endocarditis
|
10.0%
1/10
|
0.00%
0/12
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/10
|
8.3%
1/12
|
|
Infections and infestations
Septic shock
|
0.00%
0/10
|
8.3%
1/12
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/10
|
8.3%
1/12
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/10
|
8.3%
1/12
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/10
|
8.3%
1/12
|
|
Vascular disorders
Hypertension
|
0.00%
0/10
|
8.3%
1/12
|
Other adverse events
| Measure |
Daptomycin
n=10 participants at risk
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.
|
Daptomycin Plus Gentamicin
n=12 participants at risk
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.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
20.0%
2/10
|
0.00%
0/12
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/10
|
8.3%
1/12
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/10
|
8.3%
1/12
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
10.0%
1/10
|
0.00%
0/12
|
|
Vascular disorders
Hypertension
|
10.0%
1/10
|
8.3%
1/12
|
|
Vascular disorders
Hypotension
|
10.0%
1/10
|
8.3%
1/12
|
|
Vascular disorders
Phlebitis
|
10.0%
1/10
|
0.00%
0/12
|
|
Blood and lymphatic system disorders
Anaemia
|
20.0%
2/10
|
8.3%
1/12
|
|
Blood and lymphatic system disorders
Splenomegaly
|
0.00%
0/10
|
8.3%
1/12
|
|
Ear and labyrinth disorders
Hypoacusis
|
10.0%
1/10
|
0.00%
0/12
|
|
Eye disorders
Abnormal sensation in eye
|
10.0%
1/10
|
0.00%
0/12
|
|
Eye disorders
Eye pain
|
10.0%
1/10
|
0.00%
0/12
|
|
Eye disorders
Vision blurred
|
10.0%
1/10
|
0.00%
0/12
|
|
Gastrointestinal disorders
Constipation
|
40.0%
4/10
|
25.0%
3/12
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/10
|
16.7%
2/12
|
|
Gastrointestinal disorders
Nausea
|
10.0%
1/10
|
16.7%
2/12
|
|
Gastrointestinal disorders
Umbilical hernia
|
10.0%
1/10
|
0.00%
0/12
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
1/10
|
8.3%
1/12
|
|
General disorders
Catheter related complication
|
30.0%
3/10
|
8.3%
1/12
|
|
General disorders
Chest discomfort
|
10.0%
1/10
|
0.00%
0/12
|
|
General disorders
Chills
|
10.0%
1/10
|
0.00%
0/12
|
|
General disorders
Influenza like illness
|
0.00%
0/10
|
8.3%
1/12
|
|
General disorders
Malaise
|
10.0%
1/10
|
0.00%
0/12
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/10
|
8.3%
1/12
|
|
General disorders
Oedema peripheral
|
20.0%
2/10
|
0.00%
0/12
|
|
General disorders
Pyrexia
|
20.0%
2/10
|
0.00%
0/12
|
|
Infections and infestations
Bacterial sepsis
|
0.00%
0/10
|
8.3%
1/12
|
|
Infections and infestations
Escherichia urinary tract infection
|
0.00%
0/10
|
8.3%
1/12
|
|
Infections and infestations
Fungal skin infection
|
10.0%
1/10
|
0.00%
0/12
|
|
Infections and infestations
Hepatitis C
|
0.00%
0/10
|
8.3%
1/12
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/10
|
8.3%
1/12
|
|
Infections and infestations
Paronychia
|
10.0%
1/10
|
0.00%
0/12
|
|
Injury, poisoning and procedural complications
Contusion
|
10.0%
1/10
|
0.00%
0/12
|
|
Injury, poisoning and procedural complications
Procedural pain
|
10.0%
1/10
|
0.00%
0/12
|
|
Injury, poisoning and procedural complications
Wound
|
10.0%
1/10
|
0.00%
0/12
|
|
Investigations
Aspartate aminotransferase increased
|
10.0%
1/10
|
0.00%
0/12
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/10
|
8.3%
1/12
|
|
Investigations
Blood creatinine increased
|
10.0%
1/10
|
0.00%
0/12
|
|
Investigations
Blood glucose increased
|
0.00%
0/10
|
8.3%
1/12
|
|
Investigations
Cardiac murmur
|
0.00%
0/10
|
8.3%
1/12
|
|
Investigations
Haematocrit decreased
|
10.0%
1/10
|
0.00%
0/12
|
|
Investigations
Haemoglobin decreased
|
10.0%
1/10
|
0.00%
0/12
|
|
Investigations
Hepatic enzyme increased
|
10.0%
1/10
|
0.00%
0/12
|
|
Investigations
Red blood cell count decreased
|
10.0%
1/10
|
0.00%
0/12
|
|
Investigations
White blood cell count increased
|
10.0%
1/10
|
0.00%
0/12
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.00%
0/10
|
8.3%
1/12
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
10.0%
1/10
|
16.7%
2/12
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
10.0%
1/10
|
0.00%
0/12
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
10.0%
1/10
|
0.00%
0/12
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
20.0%
2/10
|
16.7%
2/12
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
10.0%
1/10
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
10.0%
1/10
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
10.0%
1/10
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.0%
1/10
|
0.00%
0/12
|
|
Nervous system disorders
Dysgeusia
|
10.0%
1/10
|
0.00%
0/12
|
|
Nervous system disorders
Headache
|
20.0%
2/10
|
0.00%
0/12
|
|
Nervous system disorders
Somnolence
|
10.0%
1/10
|
0.00%
0/12
|
|
Psychiatric disorders
Agitation
|
0.00%
0/10
|
8.3%
1/12
|
|
Psychiatric disorders
Anxiety
|
40.0%
4/10
|
8.3%
1/12
|
|
Psychiatric disorders
Insomnia
|
10.0%
1/10
|
8.3%
1/12
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/10
|
8.3%
1/12
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/10
|
8.3%
1/12
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
10.0%
1/10
|
0.00%
0/12
|
Additional Information
Ed Campanaro / Vice President, Clinical Operations
Cubist Pharmaceuticals
Phone: 781-860-8318
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER