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

NCT01728376 | Completed Phase 4 Results DMC

• 2 other identifiers: 3009-005DAP-PEDBAC-11-02
• Study Type: interventional
• Target: 82
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Bacteremia

Outcome Measures

Primary Outcomes (5)

• Number of Participants With One or More Adverse Events (AEs)

  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.

  Administration of first dose through the last follow-up visit (up to 77 days)

• Number of Participants With One or More Serious Adverse Events (SAEs)

  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.

  Administration of first dose through the last follow-up visit (up to 77 days)

• Percentage of Participants With Maximum Post-Baseline Creatine Phosphokinase (CPK) Elevations Above Upper Limit of Normal

  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) .

  Baseline up to end of therapy visit (up to 49 days)

• Percentage of Participants With Sustained CPK Elevations

  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)

  Baseline up to end of therapy visit (up to 44 days)

• Number of Participants With Abnormal Focused (Peripheral) Neurological Assessments at Test of Cure (TOC)

  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.

  TOC Safety Visit (up to 56 days)

Secondary Outcomes (4)

• Percentage of Participants With Clinical Success at TOC/Safety Visit

  7-14 days after the last dose of study medication (up to 56 days)

• Percentage of Participants With Overall Success at TOC Visit

  7-14 days after the last dose of study medication (up to 56 days)

• Trough Plasma Concentration of Daptomycin

  Days 3, 4, 5 or 6 of treatment at pre-dose

• Maximum Plasma Concentration (Cmax) of Daptomycin

  Days 3, 4, 5 or 6 of treatment at end of infusion

Study Arms (6)

Daptomycin - 12 to 17 year olds

EXPERIMENTAL

Participants ages 12-17 years old were administered daptomycin 7 mg/kg infused once daily, intravenously (IV), over 30 minutes; therapy duration (uncomplicated bacteremia) = 5-28 days, therapy duration (complicated bacteremia) = 7-42 days. After conclusion of IV therapy, can continue on oral therapy (not daptomycin, but at discretion of investigator).

Drug: Daptomycin

Comparator - 12 to 17 year olds

ACTIVE COMPARATOR

Participants ages 12-17 years old received IV vancomycin or semi-synthetic penicillin or first-generation cephalosporins or clindamycin, given as per local guidelines or site-specific prescribing information; therapy duration (uncomplicated bacteremia) = 5-28 days, therapy duration (complicated bacteremia) = 7-42 days. IV comparator and subsequent oral therapy were at the discretion of the investigator.

Drug: Comparator

Daptomycin - 7 to 11 year olds

EXPERIMENTAL

Participants ages 7 to 11 years old were administered daptomycin 9 mg/kg, infused once daily, IV over 30 minutes; therapy duration (uncomplicated bacteremia) = 5-28 days, therapy duration (complicated bacteremia) = 7-28 days. After conclusion of IV therapy, can continue on oral therapy (not daptomycin, but at discretion of investigator).

Drug: Daptomycin

Daptomycin - 1 to 6 year olds

EXPERIMENTAL

Participants ages 1 to 6 years old were administered daptomycin 12 mg/kg, infused once daily, IV over 60 minutes; therapy duration (uncomplicated bacteremia) = 5-28 days, therapy duration (complicated bacteremia) = 7-28 days. After conclusion of IV therapy, can continue on oral therapy (not daptomycin, but at discretion of investigator).

Drug: Daptomycin

Comparator - 7 to 11 year olds

ACTIVE COMPARATOR

Participants ages 7-11 years old received IV vancomycin, or semi-synthetic penicillin, or first-generation cephalosporins, clindamycin; given as per local guidelines or site-specific prescribing information; therapy duration (uncomplicated bacteremia) = 5-28 days, therapy duration (complicated bacteremia) = 7-28 days. IV comparator and subsequent oral therapy were at the discretion of the investigator.

Drug: Comparator

Comparator - 1 to 6 year olds

ACTIVE COMPARATOR

Participants ages 1-6 years old received IV vancomycin, or semi-synthetic penicillin, or first-generation cephalosporins, clindamycin; given as per local guidelines or site-specific prescribing information; therapy duration (uncomplicated bacteremia) = 5-28 days, therapy duration (complicated bacteremia) = 7-28 days. IV comparator and subsequent oral therapy were at the discretion of the investigator.

Drug: Comparator

Interventions

Daptomycin DRUG

Intravenous daptomycin given at 7 mg/kg (ages 12-17 years); 9 mg/kg (ages 7-11 years); 12 mg/kg (ages 1-6 years) infused once daily, intravenously, over 30 or 60 minutes. Participants may be switched to oral therapy following completion of IV study drug administration provided they showed clear clinical improvement and the pathogen was susceptible to an oral agent.

Also known as: Cubicin

Daptomycin - 1 to 6 year olds; Daptomycin - 12 to 17 year olds; Daptomycin - 7 to 11 year olds

Comparator DRUG

Vancomycin, Semi-synthetic penicillin, First-generation cephalosporins, Clindamycin: administered per standard of care. Participants may be switched to oral therapy following completion of IV study drug administration provided they showed clear clinical improvement and the pathogen was susceptible to an oral agent.

Comparator - 1 to 6 year olds; Comparator - 12 to 17 year olds; Comparator - 7 to 11 year olds

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• To be included in this study, participants must:
• Sign a parental consent form; if appropriate, sign an assent form
• Be between 1 and 17 years of age
• Have proven or probable bacteremia caused by S. aureus based on the traditional culture result, rapid diagnostic test or Gram stain
• If female of childbearing potential, must not be pregnant or nursing and take appropriate measures to not get pregnant during the study
• If male, must take appropriate measures to not get partner pregnant
• Able to comply with the protocol requirements

You may not qualify if:

• Participants will not be allowed into the study if they:
• Have received a certain amount of antibacterial therapy specific for current bacteremia unless it is demonstrated that the organism is resistant to the given antibacterial;
• Anticipate to require other antibiotics that may be potentially effective against S. aureus;
• Have shock or hypotension unresponsive to standard therapy;
• Have received an investigational product or have participated in an experimental procedure within 30 days;
• Have an intolerance or hypersensitivity to daptomycin;
• Have renal insufficiency;
• Have prior history or current evidence of muscle damage (rhabdomyolysis; significant CPK elevation);
• Have history of clinically significant muscular disease, nervous system or seizure disorder, including unexplained muscular weakness, history of peripheral neuropathy, Guillain-Barré or spinal cord injury;
• Have S. aureus pneumonia, empyema, meningitis, or endocarditis

Sponsors & Collaborators

• Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Related Publications (1)

• Arrieta AC, Bradley JS, Popejoy MW, Bensaci M, Grandhi A, Bokesch P, Glasser C, Du L, Patino H, Kartsonis NA. Randomized Multicenter Study Comparing Safety and Efficacy of Daptomycin Versus Standard-of-care in Pediatric Patients With Staphylococcal Bacteremia. Pediatr Infect Dis J. 2018 Sep;37(9):893-900. doi: 10.1097/INF.0000000000001926.

  PMID: 29406465 DERIVED

MeSH Terms

Conditions

Bacteremia

Interventions

Daptomycin

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2012
• First Posted: November 19, 2012
• Study Start: November 29, 2012
• Primary Completion: January 20, 2016
• Study Completion: January 20, 2016
• Last Updated: August 28, 2018
• Results First Posted: December 7, 2016

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share