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Complicated Skin and Skin Structure InfectionsPhase 4RENSENCT01104662

Study of Daptomycin Safety and Efficacy for Complicated Skin and Skin Structure Infections (cSSSI) and Bacteremia in Renal Impairment

A Phase 4 study testing Vancomycin, Daptomycin and Semi-Synthetic Penicillin in people with Complicated Skin and Skin Structure Infections and S. Aureus Bacteremia, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 10 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a multicenter, randomized, evaluator-blinded, comparator-controlled study. Participants were to be randomized (1:1) to daptomycin or comparator, stratified by degree of renal impairment (creatinine clearance [CLcr] 30 - 50 milliliters per minute [mL/min] [moderate impairment] and <30 mL/min [severe… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Vancomycin, Daptomycin and Semi-Synthetic Penicillin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
92 participants
Where
10 sitesUnited States
Study dates
19 Apr 2010to 12 Jun 2012
Phase
Phase 4
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent
  • Male or female ≥18 years of age
  • Diagnosis of cSSSI or Staphylococcus aureus (S. aureus) bacteremia
  • Renal impairment of CLcr of 30 - 50 mL/min or CLcr <30 mL/min per Cockcroft-Gault equation using actual body weight
  • Functioning hemodialysis access and on stable regimen for those receiving dialysis
  • In appropriate health for the study with no acute or chronic illnesses that could adversely impact safety or ability to complete the study
Show all 13Show fewer
  • Specific inclusion criteria for cSSSI:
  • Presence of a wound infection, major abscess, severe carbunculosis, infected ulcers, dialysis access site infection, or other type of infection in presence of complicating factor
  • At least 3 of the following symptoms, signs, or laboratory values of a skin infection: elevated temperature; elevated white blood cell (WBC) count; pain; tenderness; swelling; erythema greater than 1 centimeter (cm) beyond wound edge; induration; pus formation
  • Evidence of a Gram-positive infecting pathogen as indicated by positive Gram stain or culture obtained within 96 hours prior to study drug administration
  • Infection of sufficient severity to require parenteral antimicrobial therapy
  • Specific inclusion criteria for S. aureus bacteremia:
  • Documented S. aureus bacteremia defined as at least one positive blood culture for S. aureus obtained within 96 hours prior to the first dose of study medication

Who cannot join

  • Pregnant or lactating females, or unwilling to practice barrier methods of birth control
  • Received an investigational drug (including experimental biologic agents) within 30 days of study entry
  • Unable to discontinue use of HMG-CoA reductase inhibitor therapy while on study
  • Known allergy or intolerance to daptomycin, penicillin, or vancomycin
  • Active intravenous (IV) drug abuse
  • Confirmed or suspected osteomyelitis, septic arthritis, meningitis, epidural abscess, intra-abdominal infection, pneumonia, or infective endocarditis
Show all 40Show fewer
  • Required use of non-study systemic antibacterial agent with activity against target pathogen
  • History of muscular disease
  • Neurological disease except stroke >6 months prior to study entry
  • Intramuscular injection within 7 days of study drug administration
  • Moribund clinical condition (high likelihood of death during next 3 days)
  • Shock or hypotension (supine systolic blood pressure <80 millimeters of mercury [mmHg])
  • Body mass index (BMI) <18 or >40 kilograms per meter squared (kg/m^2) [BMI = weight (kg)/height (m^2)]
  • Known human immunodeficiency virus (HIV) infection with CD4 count ≤200 cells/millimeter (mm)^3
  • Neutropenic participants with an absolute neutrophil count ≤500 cells/mm^3
  • Anticipated to develop neutropenia absolute neutrophil count ≤500 due to prior or planned chemotherapy
  • Alanine aminotransferase (ALT) value >3 × upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) value >3 × ULN
  • Total bilirubin values ≥ 1.5 x ULN associated with ALT values >3 x ULN
  • Creatine phosphokinase (CPK) value >2 × ULN
  • Hemoglobin <8 grams per deciliter (gm/dL)
  • Unlikely to comply with study procedures or to return for evaluations
  • History of rhabdomyolysis
  • Prior enrollment into this study
  • Infections caused by Gram-positive pathogens known to be resistant to daptomycin or selected comparator agent
  • Specific exclusion criteria for cSSSI:
  • Minor or superficial skin infections as the primary site of infection
  • Cellulitis or erysipelas not associated with complicating factor as primary site of infection
  • Perirectal abscess, hidradenitis suppurativa, concomitant gangrene, myositis, multiple infected ulcers at distant sites, necrotizing fasciitis, or infected third-degree burn wounds
  • Infections requiring emergency surgery
  • Infections suspected or documented to be due exclusively to gram-negative, anaerobic, or fungal organism
  • Confirmed or suspected disorder that could interfere with the evaluations (for example, primary skin disorders)
  • Use of a topical antibiotic at the site of the infection
  • Use of systemic antibacterial therapy for the infection for >24 hours within 48 hours prior to start of study drug unless (a) infecting Gram-positive pathogen resistant to therapy or (b) therapy administered for 3 or more days with worsening or no improvement
  • Planned surgical treatment that is considered curative of the infection
  • Specific exclusion criteria for S. aureus bacteremia:
  • Has intravascular foreign material at the time the positive blood culture was drawn (for example., intracardiac pacemaker wires, percutaneous or implanted venous catheters, vascular grafts) unless material removed within 4 days after first dose of study medication or approval of medical monitor (exceptions: vascular stents in place for >6 months, permanent pacemaker attached via epicardial leads, or any dialysis access device unless this material is felt to be infected)
  • Prosthetic heart valve
  • Cardiac decompensation or valve damage or both with high likelihood of valve surgery in the 3 days after randomization
  • Polymicrobial blood infection

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites
  • Study site

    Azusa, California

  • Study site

    Columbus, Ohio

  • Study site

    Decatur, Georgia

  • Study site

    Los Angeles, California

  • Study site

    Mission, Texas

  • Study site

    Somers Point, New Jersey

  • Study site

    Torrance, California

  • Study site

    Washington D.C., District of Columbia

  • Study site

    West Reading, Pennsylvania

  • Study site

    Winston-Salem, North Carolina

Other trials in United States

About this study

Official title: A Prospective, Multicenter, Randomized, Evaluator-blinded, Comparator-controlled Study to Describe the Safety and Efficacy of Daptomycin for the Treatment of Complicated Skin and Skin Structure Infections (cSSSI) and Staphylococcus Aureus Bacteremia Among Subjects With Moderate or Severe Renal Impairment

This is a multicenter, randomized, evaluator-blinded, comparator-controlled study. Participants were to be randomized (1:1) to daptomycin or comparator, stratified by degree of renal impairment (creatinine clearance [CLcr] 30 - 50 milliliters per minute [mL/min] [moderate impairment] and <30 mL/min [severe impairment]) and by type of infection (bacteremia and complicated skin and skin structure infections [cSSSI]) to create 4 cohorts defined as follows:

  • Cohort 1: Bacteremia and CLcr <30 mL/min
  • Cohort 2: Bacteremia and CLcr 30 - 50 mL/min
  • Cohort 3: cSSSI and CLcr <30 mL/min
  • Cohort 4: cSSSI and CLcr 30 - 50 mL/min

Participants will be treated and evaluated for safety and microbiological and clinical efficacy in accordance with their type of infection and degree of renal impairment. Peak and trough samples will be collected to assess exposure to daptomycin for participants on Day 1 and following the 5th dose.

Being tested
Vancomycin, Daptomycin, Semi-Synthetic Penicillin
Medical subject headings
Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VancomycinDrug

  • DaptomycinDrug

    Also called Cubicin

  • Semi-Synthetic PenicillinDrug

    Also called SSP, nafcillin, oxacillin, cloxacillin

Study groups in NCT01104662
Study groupRoleWhat they receive
Daptomycin, Bacteremia, Severe Renal ImpairmentExperimentalCohort 1. Daptomycin was given intravenously 6 milligrams per kilogram (mg/kg) per administration. For bacteremia participants with Creatinine Clearance (CLcr) below 30 milliliters per minute (mL/min) and currently receiving hemodialysis, daptomycin was administered immediately following each hemodialysis session (3 per week) for 14 to 42 days based on disease resolution or Investigator discretion. For participants not receiving dialysis, daptomycin was administered every 48 hours for 14 to 42 days based on disease resolution or Investigator discretion.
Receives: Drug: Daptomycin
Vancomycin or SSP, Bacteremia, Severe Renal ImpairmentActive comparatorCohort 1. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by Methicillin-Susceptible Staphylococcus Aureus (MSSA) could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator's discretion. All treatments were dosed per Investigator's discretion and were administered intravenously (IV) until end of antibiotic therapy for bacteremia or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Receives: Drug: Vancomycin; Drug: Semi-Synthetic Penicillin
Daptomycin, Bacteremia, Moderate Renal ImpairmentExperimentalCohort 2. Daptomycin was given intravenously 6 milligrams per kilogram (mg/kg) per administration. For bacteremia participants with CLcr values between 30 and 50 mL/min not receiving dialysis, daptomycin was administered every 24 hours for 14 to 42 days based on disease resolution or Investigator discretion.
Receives: Drug: Daptomycin
Vancomycin or SSP , Bacteremia, Moderate Renal ImpairmentActive comparatorCohort 2. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by MSSA could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator's discretion. All treatments were dosed per Investigator's discretion and were administered IV until end of antibiotic therapy for bacteremia or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Receives: Drug: Vancomycin; Drug: Semi-Synthetic Penicillin
Daptomycin, cSSSI, Severe Renal ImpairmentExperimentalCohort 3. Daptomycin was given intravenously 4 milligrams per kilogram (mg/kg) per administration. For cSSSI participants with CLcr below 30 mL/min and currently receiving hemodialysis, daptomycin was administered immediately following each hemodialysis session (3 per week) for 7 to 14 days based on disease resolution or Investigator discretion. For participants not receiving dialysis, daptomycin was administered every 48 hours for 7 to 14 days based on disease resolution or Investigator discretion.
Receives: Drug: Daptomycin
Vancomycin or SSP , cSSSI, Severe Renal ImpairmentActive comparatorCohort 3. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by MSSA could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator's discretion. All treatments were dosed per Investigator's discretion and were administered IV until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Receives: Drug: Vancomycin; Drug: Semi-Synthetic Penicillin
Daptomycin, cSSSI, Moderate Renal ImpairmentExperimentalCohort 4. Daptomycin was given intravenously 4 milligrams per kilogram (mg/kg) per administration. For cSSSI participants with CLcr values between 30 and 50 mL/min not receiving dialysis, daptomycin was administered every 24 hours for 7 to 14 days based on disease resolution or Investigator discretion.
Receives: Drug: Daptomycin
Vancomycin or SSP , cSSSI, Moderate Renal ImpairmentActive comparatorCohort 4. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by MSSA could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator's discretion. All treatments were dosed per Investigator's discretion and were administered IV until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Receives: Drug: Vancomycin; Drug: Semi-Synthetic Penicillin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Treatment-emergent Creatine Phosphokinase (CPK) Elevations Through End of Therapy/Early Termination (EOT/ET)

    The number of participants with CPK elevations of >500 units per liter (U/L) above baseline at any time from Day 1 through the EOT/ET visit are presented.

    Measured: Baseline through EOT/ET

Secondary outcomes (1)
  1. Overall Therapeutic Outcome at Test of Cure (TOC)/Safety Visit

    Participants were assigned a Sponsor-assessed clinical outcome based on the following definitions at the TOC/Safety visit:

    Failure: Assessed as a failure at any time by the Investigator or received non-study antimicrobial therapy for lack of efficacy or had the primary site of infection removed completely by surgery or underwent surgery to treat the infection >4 days after starting study medication.

    Success: Were not assessed as a failure at any time and were assessed as a cure or improvement by the Investigator at the TOC visit.

    Non-evaluable: Received potentially effective antimicrobial therapy during the study period for reasons other than lack of efficacy or received <4 days of study medication or were not assessed by the Investigator.

    Measured: Baseline through TOC/Safety Visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2010 (estimated)
  2. Study start19 Apr 2010
  3. Primary completion12 Jun 2012
  4. Study completion12 Jun 2012

Why it stopped: Cubist has reached an agreement with the FDA that enrollment in the DAP-RENSE-08-05 study can stop.

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
92 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01104662
Sponsor's protocol ID
3009-022
Other IDs
DAP-RENSE-08-05
Acronym
RENSE
Status last verified
Aug 2018
First submitted
2 Apr 2010
Last updated
5 Sep 2018
Data monitoring committee
No
Individual data sharing
Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Vancomycin, Daptomycin and Semi-Synthetic Penicillin in people with Complicated Skin and Skin Structure Infections and S. Aureus Bacteremia, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 10 sites in United States.

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 13 inclusion and 40 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: stopped early, as of the sponsor's last update on 5 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 13 May 2015). 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?

Number of Participants With Treatment-emergent Creatine Phosphokinase (CPK) Elevations Through End of Therapy/Early Termination (EOT/ET) (time frame: Baseline through EOT/ET). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 5 Sep 2018.

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