Trial Outcomes & Findings for A Phase 3 Telavancin Staphylococcus Aureus (S. Aureus) Bacteremia Trial (NCT NCT02208063)

NCT ID: NCT02208063

Last Updated: 2020-02-17

Results Overview

The efficacy endpoint of clinical outcome of cure at the test of cure (TOC) was determined by subjects who meet all of the following criteria, as determined by the investigator and adjudicated by the blinded independent efficacy adjudication committee (IEAC). 1. Alive at TOC 2. Resolution of all clinical signed and symptoms of the Staphylococcus aureus (S. aureus) infection at TOC 3. No evidence of microbiological persistence of relapse 4. No new foci of metastatic S. aureus infection after Day 8

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

121 participants

Primary outcome timeframe

Up to 8 weeks

Results posted on

2020-02-17

Participant Flow

Participant milestones

Participant milestones
Measure	Telavancin 7.5 mg/kg administered intravenously once every 24 hours daily over 60 minutes Telavancin	Standard of Care Vancomycin, Daptomycin, synthetic penicillin or Cefazolin Vancomycin Daptomycin Synthetic penicillin Cefazolin
Overall Study STARTED	60	61
Overall Study Randomized and Treated	58	60
Overall Study Microbiological All Treated	47	52
Overall Study COMPLETED	48	50
Overall Study NOT COMPLETED	12	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Telavancin 7.5 mg/kg administered intravenously once every 24 hours daily over 60 minutes Telavancin	Standard of Care Vancomycin, Daptomycin, synthetic penicillin or Cefazolin Vancomycin Daptomycin Synthetic penicillin Cefazolin
Overall Study Death	3	5
Overall Study Not Specified in report	3	4
Overall Study Withdrawal by Subject	5	2
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

A Phase 3 Telavancin Staphylococcus Aureus (S. Aureus) Bacteremia Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Telavancin n=57 Participants 7.5 mg/kg administered intravenously once every 24 hours daily over 60 minutes Telavancin	Standard of Care n=60 Participants Vancomycin, Daptomycin, synthetic penicillin or Cefazolin Vancomycin Daptomycin Synthetic penicillin Cefazolin	Total n=117 Participants Total of all reporting groups
Age, Continuous	52.3 years STANDARD_DEVIATION 16.41 • n=99 Participants	56.5 years STANDARD_DEVIATION 16.33 • n=107 Participants	54.5 years STANDARD_DEVIATION 16.44 • n=206 Participants
Sex: Female, Male Female	18 Participants n=99 Participants	17 Participants n=107 Participants	35 Participants n=206 Participants
Sex: Female, Male Male	39 Participants n=99 Participants	43 Participants n=107 Participants	82 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	20 Participants n=99 Participants	19 Participants n=107 Participants	39 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=99 Participants	41 Participants n=107 Participants	78 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	3 Participants n=99 Participants	3 Participants n=107 Participants	6 Participants n=206 Participants
Race/Ethnicity, Customized Black or African American	8 Participants n=99 Participants	5 Participants n=107 Participants	13 Participants n=206 Participants
Race/Ethnicity, Customized White	44 Participants n=99 Participants	48 Participants n=107 Participants	92 Participants n=206 Participants
Race/Ethnicity, Customized Other	2 Participants n=99 Participants	2 Participants n=107 Participants	4 Participants n=206 Participants
Race/Ethnicity, Customized Missing	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants

PRIMARY outcome

Timeframe: Up to 8 weeks

Population: One subject enrolled was excluded from all summaries and analyses because the subject was randomized to a higher dose of telavancin (10mg/kg) that the remainder of the subjects.

Outcome measures

Outcome measures
Measure	Telavancin n=47 Participants 7.5 mg/kg administered intravenously once every 24 hours daily over 60 minutes Telavancin	Standard of Care n=52 Participants Vancomycin, Daptomycin, synthetic penicillin or Cefazolin Vancomycin Daptomycin Synthetic penicillin Cefazolin
Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC) Cure	22 Participants	27 Participants
Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC) Failure	19 Participants	21 Participants
Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC) Indeterminate	6 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: One subject enrolled was excluded from all summaries and analyses because the subject was randomized to a higher dose of telavancin (10mg/kg) that the remainder of the subjects.

The efficacy endpoint of Investigator clinical outcome of cure at the test of cure (TOC) was determined by the following criteria: 1. Subject alive at TOC 2. Resolution of all clinical signs and symptoms of the S. aureus infection at TOC (unless explained by a more likely alternative diagnosis) 3. No evidence of microbiological persistence or relapse 4. No new foci of metastatic S. aureus infection after Day 8

Outcome measures

Outcome measures
Measure	Telavancin n=47 Participants 7.5 mg/kg administered intravenously once every 24 hours daily over 60 minutes Telavancin	Standard of Care n=52 Participants Vancomycin, Daptomycin, synthetic penicillin or Cefazolin Vancomycin Daptomycin Synthetic penicillin Cefazolin
Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population Cure	26 Participants	31 Participants
Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population Failure	15 Participants	19 Participants
Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population Indeterminate	3 Participants	0 Participants
Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population Missing	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: One subject enrolled was excluded from all summaries and analyses because the subject was randomized to a higher dose of telavancin (10mg/kg) that the remainder of the subjects.

This efficacy endpoint was determined to be a clinical failure if the subject switched study antibiotic due to lack of clinical response

Outcome measures

Outcome measures
Measure	Telavancin n=47 Participants 7.5 mg/kg administered intravenously once every 24 hours daily over 60 minutes Telavancin	Standard of Care n=52 Participants Vancomycin, Daptomycin, synthetic penicillin or Cefazolin Vancomycin Daptomycin Synthetic penicillin Cefazolin
Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population Success	28 Participants	36 Participants
Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population Failure	13 Participants	15 Participants
Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population Indeterminate	5 Participants	0 Participants
Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population Missing	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 8

Population: One subject enrolled was excluded from all summaries and analyses because the subject was randomized to a higher dose of telavancin (10mg/kg) that the remainder of the subjects.

After Day 8, any sign or symptom leading to a subsequent confirmed diagnosis of a new metastatic foci of S. aureus infection

Outcome measures

Outcome measures
Measure	Telavancin n=47 Participants 7.5 mg/kg administered intravenously once every 24 hours daily over 60 minutes Telavancin	Standard of Care n=52 Participants Vancomycin, Daptomycin, synthetic penicillin or Cefazolin Vancomycin Daptomycin Synthetic penicillin Cefazolin
Number of Participants With the Development of a New Metastatic Foci of S. Aureus Infection at Test of Cure (TOC) in the Microbiological All-treated (mAT) Populations Yes	6 Participants	3 Participants
Number of Participants With the Development of a New Metastatic Foci of S. Aureus Infection at Test of Cure (TOC) in the Microbiological All-treated (mAT) Populations No	32 Participants	41 Participants
Number of Participants With the Development of a New Metastatic Foci of S. Aureus Infection at Test of Cure (TOC) in the Microbiological All-treated (mAT) Populations Indeterminate	9 Participants	8 Participants

Adverse Events

Telavancin

Serious events: 16 serious events

Other events: 29 other events

Deaths: 3 deaths

Standard of Care

Serious events: 13 serious events

Other events: 25 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Telavancin n=58 participants at risk 7.5 mg/kg administered intravenously once every 24 hours daily over 60 minutes Telavancin	Standard of Care n=60 participants at risk Vancomycin, Daptomycin, synthetic penicillin or Cefazolin Vancomycin Daptomycin Synthetic penicillin Cefazolin
Blood and lymphatic system disorders Anaemia	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Cardiac disorders Cardiac failure	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Cardiac disorders Cardiovascular insufficiency	1.7% 1/58 • Number of events 1 • 38 months	0.00% 0/60 • 38 months
General disorders Multi-organ failure	1.7% 1/58 • Number of events 1 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
General disorders Non-cardiac chest pain	1.7% 1/58 • Number of events 1 • 38 months	0.00% 0/60 • 38 months
General disorders Pyrexia	1.7% 1/58 • Number of events 1 • 38 months	0.00% 0/60 • 38 months
General disorders Unintentional medical device removal	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Infections and infestations Bacteraemia	0.00% 0/58 • 38 months	3.3% 2/60 • Number of events 2 • 38 months
Infections and infestations Osteomyelitis	3.4% 2/58 • Number of events 2 • 38 months	0.00% 0/60 • 38 months
Infections and infestations Sepsis	1.7% 1/58 • Number of events 1 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Infections and infestations Arthritis bacterial	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Infections and infestations Cellulitis	1.7% 1/58 • Number of events 1 • 38 months	0.00% 0/60 • 38 months
Infections and infestations Escherichia bacteraemia	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Infections and infestations Extradural abscess	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Infections and infestations Pneumonia	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Infections and infestations Septic shock	1.7% 1/58 • Number of events 1 • 38 months	0.00% 0/60 • 38 months
Infections and infestations Serratia infection	1.7% 1/58 • Number of events 1 • 38 months	0.00% 0/60 • 38 months
Infections and infestations Spinal empyema	1.7% 1/58 • Number of events 1 • 38 months	0.00% 0/60 • 38 months
Investigations Blood creatinine increased	1.7% 1/58 • Number of events 1 • 38 months	0.00% 0/60 • 38 months
Investigations Electrocardiogram QT prolonged	1.7% 1/58 • Number of events 1 • 38 months	0.00% 0/60 • 38 months
Investigations Hepatic enzyme increased	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Investigations Liver function test abnormal	1.7% 1/58 • Number of events 1 • 38 months	0.00% 0/60 • 38 months
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant peritoneal neoplasm	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Nervous system disorders Brain oedema	1.7% 1/58 • Number of events 1 • 38 months	0.00% 0/60 • 38 months
Nervous system disorders Encephalopathy	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Renal and urinary disorders Acute kidney injury	1.7% 1/58 • Number of events 1 • 38 months	3.3% 2/60 • Number of events 2 • 38 months
Renal and urinary disorders Tubulointerstitial nephritis	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Renal and urinary disorders Urinary retention	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.7% 1/58 • Number of events 1 • 38 months	0.00% 0/60 • 38 months
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.7% 1/58 • Number of events 1 • 38 months	0.00% 0/60 • 38 months
Vascular disorders Haematoma	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months
Vascular disorders Shock	0.00% 0/58 • 38 months	1.7% 1/60 • Number of events 1 • 38 months

Other adverse events

Other adverse events
Measure	Telavancin n=58 participants at risk 7.5 mg/kg administered intravenously once every 24 hours daily over 60 minutes Telavancin	Standard of Care n=60 participants at risk Vancomycin, Daptomycin, synthetic penicillin or Cefazolin Vancomycin Daptomycin Synthetic penicillin Cefazolin
Blood and lymphatic system disorders Anaemia	10.3% 6/58 • Number of events 6 • 38 months	11.7% 7/60 • Number of events 7 • 38 months
Gastrointestinal disorders Nausea	10.3% 6/58 • Number of events 6 • 38 months	10.0% 6/60 • Number of events 6 • 38 months
Gastrointestinal disorders Constipation	5.2% 3/58 • Number of events 3 • 38 months	11.7% 7/60 • Number of events 7 • 38 months
Gastrointestinal disorders Diarrhoea	5.2% 3/58 • Number of events 3 • 38 months	10.0% 6/60 • Number of events 6 • 38 months
Metabolism and nutrition disorders Hypokalaemia	17.2% 10/58 • Number of events 10 • 38 months	13.3% 8/60 • Number of events 8 • 38 months
Nervous system disorders Headache	5.2% 3/58 • Number of events 3 • 38 months	5.0% 3/60 • Number of events 3 • 38 months
Psychiatric disorders Insomnia	8.6% 5/58 • Number of events 5 • 38 months	5.0% 3/60 • Number of events 3 • 38 months
Renal and urinary disorders Acute kidney injury	6.9% 4/58 • Number of events 4 • 38 months	13.3% 8/60 • Number of events 8 • 38 months

Additional Information

Senior Director of Clinical and Regulatory Affairs

Cumberland Pharmaceuticals Inc.

Phone: 615-255-0068

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place