OsteomyelitisPhase 2NCT00428844
Study of Daptomycin in Subjects Undergoing Surgery for Osteomyelitis Associated With an Infected Prosthetic Caused by Staphylococci
A Phase 2 study testing daptomycin, vancomycin and teicoplanin in people with Osteomyelitis, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 26 sites in 3 countries.
Trial summary
This is a research study designed to look at the efficacy and safety of daptomycin given at a dose of 6 mg/kg or 8 mg/kg in subjects being treated for prosthetic hip or knee infections caused by Staphylococci. These types of bacteria are among the most common types of bacteria causing infections of prosthetic joints. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Osteomyelitis
- What is being tested?
- daptomycin, vancomycin and teicoplanin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 26 sitesin 3 countries
- Study dates
- 26 Jun 2007to 23 Jun 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must be between the ages of 18 and 80, inclusive
- Subject must have a diagnosis of prosthetic joint infection (PJI) in a hip or knee joint which has never previously been totally revised because of an infection and for which they are anticipated to undergo a two-stage replacement surgery
- Subject must have a positive microbiological identifier of staphylococci.
- If Subject is female of childbearing potential, must be willing to practice reliable birth control
Who cannot join
- Subject has permanent intravascular prosthetic material such as heart valves or pacemakers
- Subject has a creatinine clearance (CLCR) <30 mL/min as determined by the Cockcroft-Gault equation using actual body weight.
- Subject has significant hepatic dysfunction
- Subject has a fungal or mycobacterial PJI
- Subject is known to be HIV-infected with CD4 count ≤ 200 cells/ mm3
- Subject has an abnormal creatine phosphokinase (CPK) (elevated CPK level ≥ 2x ULN) at baseline as measured by central laboratory
Show all 9Show fewer
- Subject is currently under treatment with chemotherapeutic agents excluding chronic maintenance therapy (e.g. tamoxifen to prevent relapse of primary breast cancer)
- Subject is pregnant, nursing, or lactating.
- Subject is receiving or is expected to receive chronic immunosuppressive therapy during the study.
Trial locations and contacts
26 sites in 3 countries.
26 sites in 3 countries
United States17 sites
Summa Health Systems
Akron, Ohio, 44304
Lehigh Valley Hospital Trauma and Critical Care Research
Allentown, Pennsylvania, 18103
Rush St. Luke's Medical Center
Chicago, Illinois, 60612
Cleveland Clinic
Cleveland, Ohio, 44195
South Denver Infectious Disease Associates, PC
Englewood, Colorado, 80133
Idaho Falls Infectious Diseases, PLLC
Idaho Falls, Idaho, 83404
Gundersen Clinic, LTD
La Crosse, Wisconsin, 54601
Dartmouth-Hitchcock Medical center
Lebanon, New Hampshire, 03756
Regional Infectious Diseases-Infusion Center
Lima, Ohio, 45801
UAMS College of Medicine
Little Rock, Arkansas, 72205-7199
Rothman Institute
Philadelphia, Pennsylvania, 19107
Sierra Infectious Disease
Reno, Nevada, 89502
Mayo Clinic
Rochester, Minnesota, 55905
Southern Illinois University School of Medicine
Springfield, Illinois, 62794
Infectious Disease Association of Tampa Bay
Tampa, Florida, 33606
Kane and Davis Associates
Washington D.C., District of Columbia, 20016
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Russia6 sites
Federal National Institution of Science "Russian Ilizarov Scientific Center" "Restorative Traumatology and Orthopedics" of Rosmedtechnology
Kurgan, 640014
National Healthcare Institution of Moscow "City Clinical Hospital #64"
Moscow, 117292
Federal Healthcare Institute "Novosibirsk Scientific Research Institute of Traumatology and Orthopedy Rosmeditechnology"
Novosibirsk, 630091
National Educational Institution of Higher Professional Education "Saint Petersburg State Medical Academy n.a. Mechnikov of Roszdrav"
Saint Petersburg, 195067
Russian Research Institute of Traumatology and Orthopedy
Saint Petersburg, 197046
National Healthcare Institution "Samara Regional Clinical Hospital n.a. Kalinin"
Samara, 443095
United Kingdom3 sites
The Royal Infirmary of Edinburgh at Little France
Edinburgh, Scotland, EH164SA
Brownlee Centre - Gartnavel General Hospital
Glasgow, Scotland, G120YN
Nuffield Orthopaedics Centre, Bone Infection Unit
Headington, Oxford, Oxfordshire, OX37LD
About this study
Official title: A Phase 2 Randomized Study Investigating the Safety, Efficacy and Pharmacokinetics of Daptomycin 6 mg/kg and 8 mg/kg Versus Comparator in the Treatment of Subjects Undergoing Surgical Standard of Care for Osteomyelitis Associated With an Infected Prosthetic Hip or Knee Joint Caused by Staphylococci
This is a research study designed to look at the efficacy and safety of daptomycin given at a dose of 6 mg/kg or 8 mg/kg in subjects being treated for prosthetic hip or knee infections caused by Staphylococci. These types of bacteria are among the most common types of bacteria causing infections of prosthetic joints.
- Conditions
- Osteomyelitis
- Being tested
- daptomycin, vancomycin, teicoplanin, nafcillin, oxacillin
- Keywords
- Osteomyelitis, Prosthetic Hip, Prosthetic Knee, MRSA, Osteomyelitis Associated with an Infected Prosthetic Hip or Knee Joint, Staphylococci
- Medical subject headings
- Osteomyelitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
daptomycinDrug
Also called Cubicin
6 mg/kg
daptomycinDrug
Also called Cubicin
8 mg/kg
vancomycinDrug
Also called Vancocin
1 gram
teicoplaninDrug
Also called Targocid
6 mg/kg; used only at UK sites
nafcillinDrug
Also called Unipen
1-2 gram
oxacillinDrug
Also called Bactocill
1-2 gram
flucloxacillinDrug
Also called Fluclox
1-2 mg
| Study group | Role | What they receive |
|---|---|---|
| Daptomycin 6 mg/kg | Experimental | Daptomycin (6 mg/kg every 24 hours [q24h]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week). Receives: Drug: daptomycin |
| Daptomycin 8 mg/kg | Experimental | Daptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week). Receives: Drug: daptomycin |
| Comparator | Active comparator | Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week). Receives: Drug: vancomycin; Drug: teicoplanin; Drug: nafcillin; Drug: oxacillin; Drug: flucloxacillin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L)
Number of subjects with CPK >500 U/L between Day 3 and 7 days following the last dose of study medication (Day 7P) as measured by the central laboratory.
Measured: From the 3rd day of therapy to 1 week post last dose (approximately week 7)
Secondary outcomes (5)
Safety - Notable Laboratory Abnormalities
Summary of Notable Laboratory Abnormalities - description of the proportion of subjects within each treatment group that had clinical laboratory values outside the reference range.
Measured: From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30)
Overall Clinical Outcome
The sponsor determined overall clinical outcome based on blinded review of clinical, microbiological, and radiological response of the subject including, but not limited to, clinical signs and symptoms of PJI, microbiological assessments, radiographic findings, and surgical procedures performed. Subjects were a success if both clinical and microbiological responses were success. A subject who failed to respond clinically or microbiologically was a failure. If microbiological response was non-evaluable and/or clinical evaluation at TOC was not performed, the subject was non-evaluable.
Measured: Approximately 6 weeks post last dose (approximately week 12)
Microbiological Response
Sponsor's assessment of subject-level microbiological response at the test-of-cure visit for the modified Intent-to-Treat (mITT) population.
Measured: Approximately 6 weeks post last dose (approximately week 12)
Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax)
The pharmacokinetic (PK) parameters of daptomycin at steady state for the 6 mg/kg and 8 mg/kg dose groups. On treatment day 4, PK samples for daptomycin levels were to be obtained prior to start of daptomycin infusion (0 hr) and at 0.5 hr (end of infusion), 1-1.5 hr, 3-5 hr, 8-12 hr, and 24 hr after the start of daptomycin infusion.
Measured: Day 4 (steady state)
Pharmacokinetic Parameter: Area Under the Concentration-time Curve During a Dosing Interval at Steady State (AUCss)
The pharmacokinetic (PK) parameters of daptomycin at steady state for the 6 mg/kg and 8 mg/kg dose groups. On treatment day 4, PK samples for daptomycin levels were to be obtained prior to start of daptomycin infusion (0 hr) and at 0.5 hr (end of infusion), 1-1.5 hr, 3-5 hr, 8-12 hr, and 24 hr after the start of daptomycin infusion.
Measured: Day 4 (steady state)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2007 (estimated)
- Study start26 Jun 2007
- Primary completion26 Mar 2010
- Study completion23 Jun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OsteomyelitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alistair Wheeler, MD, Study director, Cubist Pharmaceuticals, 65 Hayden Ave, Lexington, MA 02421, USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00428844
- Sponsor's protocol ID
- 3009-016
- Other IDs
- DAP-OST-06-02
- Status last verified
- Jan 2018
- First submitted
- 26 Jan 2007
- Last updated
- 31 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf http://engagezone.msd.com/ds\_documentation.php
Publications
Byren I, Rege S, Campanaro E, Yankelev S, Anastasiou D, Kuropatkin G, Evans R. Randomized controlled trial of the safety and efficacy of Daptomycin versus standard-of-care therapy for management of patients with osteomyelitis associated with prosthetic devices undergoing two-stage revision arthroplasty. Antimicrob Agents Chemother. 2012 Nov;56(11):5626-32. doi: 10.1128/AAC.00038-12. Epub 2012 Aug 20.
PubMed 22908174
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized Study Investigating the Safety, Efficacy and Pharmacokinetics of Daptomycin 6 mg/kg and 8 mg/kg Versus Comparator in the Treatment of Subjects Undergoing Surgical Standard of Care for Osteomyelitis Associated With an Infected Prosthetic Hip or Knee Joint Caused by Staphylococci
- ClinicalTrials.gov ID
- NCT00428844
- Acronym / sponsor ID
- 3009-016
- Conditions
- Osteomyelitis
- Keywords
- Osteomyelitis, Prosthetic Hip, Prosthetic Knee, MRSA, Osteomyelitis Associated with an Infected Prosthetic Hip or Knee Joint, Staphylococci
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- 26 Jun 2007 (actual)
- Primary completion
- 26 Mar 2010 (actual)
- Study completion
- 23 Jun 2010 (actual)
- First posted
- 30 Jan 2007 (estimated)
- Results
- Posted 14 Jun 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a research study designed to look at the efficacy and safety of daptomycin given at a dose of 6 mg/kg or 8 mg/kg in subjects being treated for prosthetic hip or knee infections caused by Staphylococci. These types of bacteria are among the most common types of bacteria causing infections of prosthetic joints.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Daptomycin 6 mg/kg | Experimental | Drug: daptomycinDaptomycin (6 mg/kg every 24 hours [q24h]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week). |
| Daptomycin 8 mg/kg | Experimental | Drug: daptomycinDaptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week). |
| Comparator | Active comparator | Drug: vancomycin, Drug: teicoplanin, Drug: nafcillin, Drug: oxacillin, Drug: flucloxacillinVancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Subject must be between the ages of 18 and 80, inclusive
- Subject must have a diagnosis of prosthetic joint infection (PJI) in a hip or knee joint which has never previously been totally revised because of an infection and for which they are anticipated to undergo a two-stage replacement surgery
- Subject must have a positive microbiological identifier of staphylococci.
- If Subject is female of childbearing potential, must be willing to practice reliable birth control
Key exclusion criteria (9 listed)
- Subject has permanent intravascular prosthetic material such as heart valves or pacemakers
- Subject has a creatinine clearance (CLCR) <30 mL/min as determined by the Cockcroft-Gault equation using actual body weight.
- Subject has significant hepatic dysfunction
- Subject has a fungal or mycobacterial PJI
- Subject is known to be HIV-infected with CD4 count ≤ 200 cells/ mm3
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| daptomycinAlso: Cubicin6 mg/kg | Drug | Daptomycin 6 mg/kg |
| daptomycinAlso: Cubicin8 mg/kg | Drug | Daptomycin 8 mg/kg |
| vancomycinAlso: Vancocin1 gram | Drug | Comparator |
| teicoplaninAlso: Targocid6 mg/kg; used only at UK sites | Drug | Comparator |
| nafcillinAlso: Unipen1-2 gram | Drug | Comparator |
| oxacillinAlso: Bactocill1-2 gram | Drug | Comparator |
| flucloxacillinAlso: Fluclox1-2 mg | Drug | Comparator |
Primary outcome
Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L)
Time frame: From the 3rd day of therapy to 1 week post last dose (approximately week 7)
Number of subjects with CPK >500 U/L between Day 3 and 7 days following the last dose of study medication (Day 7P) as measured by the central laboratory.
5 secondary outcomes
Safety - Notable Laboratory Abnormalities
Time frame: From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30)
Overall Clinical Outcome
Time frame: Approximately 6 weeks post last dose (approximately week 12)
Microbiological Response
Time frame: Approximately 6 weeks post last dose (approximately week 12)
Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax)
Time frame: Day 4 (steady state)
Pharmacokinetic Parameter: Area Under the Concentration-time Curve During a Dosing Interval at Steady State (AUCss)
Time frame: Day 4 (steady state)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22908174Byren I, Rege S, Campanaro E, Yankelev S, Anastasiou D, Kuropatkin G, Evans R. Randomized controlled trial of the safety and efficacy of Daptomycin versus standard-of-care therapy for management of patients with osteomyelitis associated with prosthetic devices undergoing two-stage revision arthroplasty. Antimicrob Agents Chemother. 2012 Nov;56(11):5626-32. doi: 10.1128/AAC.00038-12. Epub 2012 Aug 20.
- Individual participant dataSharing planned: Yes. http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alistair Wheeler, MD study director
Cubist Pharmaceuticals, 65 Hayden Ave, Lexington, MA 02421, USA
26 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing daptomycin, vancomycin and teicoplanin in people with Osteomyelitis, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 26 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, Russia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jun 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L) (time frame: From the 3rd day of therapy to 1 week post last dose (approximately week 7)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00428844, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2018.