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NCT01728376

Safety & Efficacy of Daptomycin Versus Standard of Care (SOC) in 1 - 17 Year Olds With Staphylococcus Aureus Bacteremia (MK-3009-005)

Completed Phase 4 Results posted Last updated 28 August 2018
What this trial tests

Phase 4 trial testing Daptomycin in Bacteremia in 82 participants. Completed in 20 January 2016.

Timeline
29 November 2012
Primary endpoint
20 January 2016
20 January 2016

Quick facts

Lead sponsorCubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment82
Start date29 November 2012
Primary completion20 January 2016
Estimated completion20 January 2016

Drugs / interventions tested

Conditions studied

Sponsor

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) — full company profile →

Who can join

Adults 1 to 17, any sex, with Bacteremia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With One or More Adverse Events (AEs) Primary · Administration of first dose through the last follow-up visit (up to 77 days)

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

GroupValue95% CI
Daptomycin - 1 to 6 Year Olds15
Comparator- 1 to 6 Year Olds6
Daptomycin - 7 to 11 Year Olds12
Comparator - 7 to 11 Year Olds9
Daptomycin - 12 to 17 Year Olds9
Comparator - 12 to 17 Year Olds5
Number of Participants With One or More Serious Adverse Events (SAEs) Primary · Administration of first dose through the last follow-up visit (up to 77 days)

An SAE is any adverse experience occurring at any dose that results in any of the following outcomes: death, life threatening experience, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is considered to be an important medical event.

GroupValue95% CI
Daptomycin - 1 to 6 Year Olds6
Comparator- 1 to 6 Year Olds2
Daptomycin - 7 to 11 Year Olds4
Comparator - 7 to 11 Year Olds3
Daptomycin - 12 to 17 Year Olds3
Comparator - 12 to 17 Year Olds2
Percentage of Participants With Maximum Post-Baseline Creatine Phosphokinase (CPK) Elevations Above Upper Limit of Normal Primary · Baseline up to end of therapy visit (up to 49 days)

Blood was drawn from baseline up to the end of therapy visit to determine the percentage of participants with maximum post-baseline CPK elevations above the upper limit of 500 Units Per Liter (U/L) .

GroupValue95% CI
Daptomycin - 1 to 6 Year Olds40.9
Comparator- 1 to 6 Year Olds40.0
Daptomycin - 7 to 11 Year Olds10.5
Comparator - 7 to 11 Year Olds0.0
Daptomycin - 12 to 17 Year Olds28.6
Comparator - 12 to 17 Year Olds14.3
Percentage of Participants With Sustained CPK Elevations Primary · Baseline up to end of therapy visit (up to 44 days)

Blood was drawn from baseline up to the end of therapy visit to determine the percentage of participants with sustained CPK elevations, defined as two consecutive post-baseline values above the upper limit of normal (ULN)

GroupValue95% CI
Daptomycin - 1 to 6 Year Olds18.2
Comparator- 1 to 6 Year Olds20.0
Daptomycin - 7 to 11 Year Olds0.0
Comparator - 7 to 11 Year Olds0.0
Daptomycin - 12 to 17 Year Olds28.6
Comparator - 12 to 17 Year Olds14.3
Number of Participants With Abnormal Focused (Peripheral) Neurological Assessments at Test of Cure (TOC) Primary · TOC Safety Visit (up to 56 days)

Focused neurological examinations were done at the TOC/Safety Visit. These examinations include assessments of sensation, pupillary reflex and tracking, peripheral reflexes (biceps, patellar tendon, ankle jerk and plantar response), muscle tone and strength (upper and lower limbs), coordination (finger to nose) and tremor of the hands/fingers.

Alertness
GroupValue95% CI
Daptomycin - 1 to 6 Year Olds0
Comparator- 1 to 6 Year Olds0
Daptomycin - 7 to 11 Year Olds0
Comparator - 7 to 11 Year Olds0
Daptomycin - 12 to 17 Year Olds0
Comparator - 12 to 17 Year Olds0
Pupillary Reflex and Tracking
GroupValue95% CI
Daptomycin - 1 to 6 Year Olds0
Comparator- 1 to 6 Year Olds0
Daptomycin - 7 to 11 Year Olds1
Comparator - 7 to 11 Year Olds0
Daptomycin - 12 to 17 Year Olds0
Comparator - 12 to 17 Year Olds0
Peripheral Reflex - Biceps
GroupValue95% CI
Daptomycin - 1 to 6 Year Olds0
Comparator- 1 to 6 Year Olds0
Daptomycin - 7 to 11 Year Olds0
Comparator - 7 to 11 Year Olds0
Daptomycin - 12 to 17 Year Olds0
Comparator - 12 to 17 Year Olds0
Peripheral Reflex - Patellar Tendon
GroupValue95% CI
Daptomycin - 1 to 6 Year Olds0
Comparator- 1 to 6 Year Olds0
Daptomycin - 7 to 11 Year Olds1
Comparator - 7 to 11 Year Olds0
Daptomycin - 12 to 17 Year Olds0
Comparator - 12 to 17 Year Olds0
Peripheral Reflex - Ankle Jerk
GroupValue95% CI
Daptomycin - 1 to 6 Year Olds0
Comparator- 1 to 6 Year Olds0
Daptomycin - 7 to 11 Year Olds1
Comparator - 7 to 11 Year Olds0
Daptomycin - 12 to 17 Year Olds0
Comparator - 12 to 17 Year Olds0
Peripheral Reflex - Plantar Response
GroupValue95% CI
Daptomycin - 1 to 6 Year Olds0
Comparator- 1 to 6 Year Olds0
Daptomycin - 7 to 11 Year Olds0
Comparator - 7 to 11 Year Olds0
Daptomycin - 12 to 17 Year Olds0
Comparator - 12 to 17 Year Olds0
Muscle Tone - Lower/Upper Limbs
GroupValue95% CI
Daptomycin - 1 to 6 Year Olds0
Comparator- 1 to 6 Year Olds0
Daptomycin - 7 to 11 Year Olds0
Comparator - 7 to 11 Year Olds0
Daptomycin - 12 to 17 Year Olds2
Comparator - 12 to 17 Year Olds0
Muscle Strength - Lower/Upper Limbs
GroupValue95% CI
Daptomycin - 1 to 6 Year Olds0
Comparator- 1 to 6 Year Olds0
Daptomycin - 7 to 11 Year Olds0
Comparator - 7 to 11 Year Olds0
Daptomycin - 12 to 17 Year Olds2
Comparator - 12 to 17 Year Olds0
Percentage of Participants With Clinical Success at TOC/Safety Visit Secondary · 7-14 days after the last dose of study medication (up to 56 days)

Clinical success was determined by assessing resolution/improvement of signs and symptoms. An assessment of cure or improved is considered clinical success. Cure: resolution of clinically significant signs and symptoms associated with admission infection; no further antibiotic therapy is required for the primary infection under study. Improvement: partial resolution of clinical signs/symptoms of infection such that no further antibiotic therapy is required for the primary infection under study.

Cured
GroupValue95% CI
Daptomycin - 1 to 6 Year Olds80.0
Comparator- 1 to 6 Year Olds87.5
Daptomycin - 7 to 11 Year Olds94.1
Comparator - 7 to 11 Year Olds77.8
Daptomycin - 12 to 17 Year Olds78.6
Comparator - 12 to 17 Year Olds60.0
Improved
GroupValue95% CI
Daptomycin - 1 to 6 Year Olds5.0
Comparator- 1 to 6 Year Olds0
Daptomycin - 7 to 11 Year Olds0
Comparator - 7 to 11 Year Olds0
Daptomycin - 12 to 17 Year Olds7.1
Comparator - 12 to 17 Year Olds0
Percentage of Participants With Overall Success at TOC Visit Secondary · 7-14 days after the last dose of study medication (up to 56 days)

Overall success is based on microbiologic responses after initiating study drug and clinical response at TOC/Safety Visit. Overall outcome is a success if both clinical and microbiologic outcomes are successes. An assessment of cure or improved is considered clinical success. Microbiological Success: a participant for whom all baseline infecting pathogens were eradicated (presumed or documented) within 7 days from the start of study drug for uncomplicated bacteremia with no source of infection present, and 10 days for complicated bacteremia or when the source of infection has not been removed.

GroupValue95% CI
Daptomycin - 1 to 6 Year Olds80.0
Comparator- 1 to 6 Year Olds75.0
Daptomycin - 7 to 11 Year Olds82.4
Comparator - 7 to 11 Year Olds44.4
Daptomycin - 12 to 17 Year Olds50.0
Comparator - 12 to 17 Year Olds60.0
Trough Plasma Concentration of Daptomycin Secondary · Days 3, 4, 5 or 6 of treatment at pre-dose

Plasma concentrations of daptomycin were measured on Days 3 through 6 of IV dosing. Trough concentrations were collected 22 to 26 hours following the end of the previous day's end of infusion and before the next infusion. Concentrations below the limit of quantification were excluded.

GroupValue95% CI
Daptomycin - 1 to 6 Year Olds4.72± 1.643
Daptomycin - 7 to 11 Year Olds6.39± 3.035
Daptomycin - 12 to 17 Year Olds14.69± 19.109
Maximum Plasma Concentration (Cmax) of Daptomycin Secondary · Days 3, 4, 5 or 6 of treatment at end of infusion

Plasma concentrations of daptomycin were measured on Days 3 through 6 of IV dosing. Peak concentrations were collected up to 15 minutes following the end of infusion. Concentrations below the limit of quantification were excluded.

GroupValue95% CI
Daptomycin - 1 to 6 Year Olds96.69± 32.946
Daptomycin - 7 to 11 Year Olds87.66± 34.992
Daptomycin - 12 to 17 Year Olds74.70± 34.909

Adverse events — posted to ClinicalTrials.gov

Time frame: Administration of first dose through the last follow-up visit (up to 77 days).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Daptomycin - 1 to 6 Year Olds
Serious: 6/22 (27%)
Deaths:
Comparator - 1 to 6 Year Olds
Serious: 2/10 (20%)
Deaths:
Daptomycin - 7 to 11 Year Olds
Serious: 4/19 (21%)
Deaths:
Comparator - 7 to 11 Year Olds
Serious: 3/9 (33%)
Deaths:
Daptomycin - 12 to 17 Year Olds
Serious: 3/14 (21%)
Deaths:
Comparator - 12 to 17 Year Olds
Serious: 2/7 (29%)
Deaths:

Serious adverse events (19 terms)

ReactionSystemDaptomycin - 1 to 6 Year O…Comparator - 1 to 6 Year O…Daptomycin - 7 to 11 Year …Comparator - 7 to 11 Year …Daptomycin - 12 to 17 Year…Comparator - 12 to 17 Year…
BacteraemiaInfections and infestations
Cardiac failure congestiveCardiac disorders
Device breakageGeneral disorders
Intestine transplant rejectionImmune system disorders
Arthritis bacterialInfections and infestations
Bone abscessInfections and infestations
Muscle abscessInfections and infestations
OsteomyelitisInfections and infestations
PneumoniaInfections and infestations
Staphylococcal bacteraemiaInfections and infestations
Hepatic enzyme increasedInvestigations
MalnutritionMetabolism and nutrition disorders
Bone fistulaMusculoskeletal and connective tissue disorders
SynovitisMusculoskeletal and connective tissue disorders
Pneumonia aspirationRespiratory, thoracic and mediastinal disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
Pulmonary oedemaRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Venous thrombosis limbVascular disorders
Other adverse events (82 terms — click to expand)

ReactionSystemDaptomycin - 1 to 6 Year O…Comparator - 1 to 6 Year O…Daptomycin - 7 to 11 Year …Comparator - 7 to 11 Year …Daptomycin - 12 to 17 Year…Comparator - 12 to 17 Year…
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
OsteomyelitisInfections and infestations
Blood creatine phosphokinase increasedInvestigations
ErythemaSkin and subcutaneous tissue disorders
Abdominal lymphadenopathyBlood and lymphatic system disorders
AnaemiaBlood and lymphatic system disorders
LymphadenopathyBlood and lymphatic system disorders
ThrombocytosisBlood and lymphatic system disorders
Ventricular extrasystolesCardiac disorders
Vision blurredEye disorders
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
Catheter site dischargeGeneral disorders
Catheter site oedemaGeneral disorders
Catheter site painGeneral disorders
Device breakageGeneral disorders
Infusion site painGeneral disorders
Drug hypersensitivityImmune system disorders
Abdominal abscessInfections and infestations
AbscessInfections and infestations
Arthritis bacterialInfections and infestations
Candida infectionInfections and infestations
CellulitisInfections and infestations
Infected skin ulcerInfections and infestations
Lung abscessInfections and infestations
NasopharyngitisInfections and infestations
Osteomyelitis acuteInfections and infestations
Postoperative wound infectionInfections and infestations
Rash pustularInfections and infestations
Rhinovirus infectionInfections and infestations
Systemic candidaInfections and infestations
VaricellaInfections and infestations
Viral infectionInfections and infestations
Arthropod biteInjury, poisoning and procedural complications
ContusionInjury, poisoning and procedural complications
ExcoriationInjury, poisoning and procedural complications
WoundInjury, poisoning and procedural complications
Wound dehiscenceInjury, poisoning and procedural complications

Most-reported serious reactions: Bacteraemia, Cardiac failure congestive, Device breakage, Intestine transplant rejection, Arthritis bacterial, Bone abscess, Muscle abscess, Osteomyelitis.

Data from ClinicalTrials.gov NCT01728376 adverse events section.

Sponsor's own description

The intent of this study is to describe the safety and efficacy of daptomycin versus standard of care (SOC) in pediatric participants aged 1-17 years with bacteremia caused by Staphylococcus aureus (S. aureus).

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Daptomycin: an evidence-based review of its role in the treatment of Gram-positive infections.
    Gonzalez-Ruiz A, Seaton RA, Hamed K. · · 2016 · cited 65× · PMID 27143941 · DOI 10.2147/idr.s99046
  2. Randomized Multicenter Study Comparing Safety and Efficacy of Daptomycin Versus Standard-of-care in Pediatric Patients With Staphylococcal Bacteremia.
    Arrieta AC, Bradley JS, Popejoy MW, Bensaci M, et al · · 2018 · cited 31× · PMID 29406465 · DOI 10.1097/inf.0000000000001926
  3. Clinical Experience with Daptomycin for the Treatment of Gram-positive Infections in Children and Adolescents.
    Syriopoulou V, Dailiana Z, Dmitriy N, Utili R, et al · · 2016 · cited 20× · PMID 26849158 · DOI 10.1097/inf.0000000000001076

Verify or expand the search:

Other trials of Daptomycin

Trials testing the same drug.

Other recruiting trials for Bacteremia

Currently open trials in the same condition.

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

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01728376.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing