Phase II, Open-Label Study to Evaluate the Safety and Efficacy of Daptomycin in the Treatment of Catheter-Related Staphylococcus Aureus Bloodstream Infections
18 Years
N/A
Both
Staphylococcus Aureus
Trial Information
Phase II, Open-Label Study to Evaluate the Safety and Efficacy of Daptomycin in the Treatment of Catheter-Related Staphylococcus Aureus Bloodstream Infections
Daptomycin is a new antibiotic. It may be effective against a variety of bacterial
infections that are difficult to treat.
Aztreonam, Cefepime, Carbapenems and Augmentin are antibiotics that are used to treat
certain types of bacteria.
If you are found to be eligible to take part in this study, you will be given daptomycin by
vein for at least 10 days, depending on your certain type of bacteria. You will receive
Daptomycin by vein for 30 minutes every 24 hours.
The CVC associated with CRBSI (catheter-related bloodstream infection = CR-BSI)from all
enrolled patients will either be removed or be exchanged over guide wire for a new CVC
within 96 hours of onset of the first blood culture. Your primary doctor will decide
whether to remove or exchange the CVC with the willingness of you.
If the study doctor and/or your primary physician knows or thinks that you have a mixed
infection (both "gram positive" and "gram negative") or may have infection in lungs
(pneumonia), you may also be treated with the antibiotic drugs Aztreonam, Cefepime,
Carbapenems, or Augmentin by vein or by mouth in combination with the study drug Daptomycin.
During each week of treatment, blood (about 1 tablespoon) will be drawn for routine lab
tests. The blood sample may be drawn from the CVC, if the CVC is still in place. In
addition, blood (about 1 tablespoon) will be drawn every other day until it no longer shows
signs of infection. The catheter exit site may be examined at each visit until you have no
more signs or symptoms of infection. If you are discharged from the hospital before
completing the study medication, arrangements will be made to provide infusions on an
out-patient basis or home infusion.
During each week of treatment, you will be asked about any symptoms or illnesses that you
have experienced. In addition, you will be asked to inform the study doctor and/or study
staff of any medications or therapies that you are taking while on study. You will be taken
off study if the infection gets worse or intolerable side effects occur.
Participation on this study will last for a no more than 60 days. If you have been
discharged from the hospital, the end of treatment visit will take place within 7 -14 days
of the last day of study drug. You will need to return for the visit on an outpatient
basis.
At this visit, you will have a physical exam, including measurement of vital signs (heart
rate, temperature, and blood pressure). Blood samples (about 1 tablespoon) will be drawn
for routine test and to check for infection. The blood sample may be drawn from the CVC, if
the CVC is still in place. The CVC exit site will be examined. You will be asked about any
symptoms or illnesses that you may have experienced. In addition, you will be asked to
inform the study doctor and/or study staff of any medications or therapies that you are
taking.
You will have a follow-up exam between 32 (+/- 7) days after your last dose of study drug.
You will have a physical exam, including measurement of vital signs (heart rate,
temperature, and blood pressure). Blood (about one tablespoon) will be drawn for routine
tests and to check for infection. The blood samples may be drawn from the CVC, if the CVC
is still in place. The CVC exit site may be examined. You will be asked about any symptoms
or illnesses that you may have experienced. In addition, you will be asked to inform the
study doctor and/or study staff of any medications or therapies that you are taking.
Participation on this study will end once you complete the follow-up visit.
This is an investigational study. Daptomycin is approved by the FDA for the treatment of
skin and soft tissue infection. However, for the use described in this study and at this
dose level, Daptomycin is authorized by the FDA for use in research only. About 50
patients will take part in this study. All will be enrolled at M. D. Anderson.
Inclusion Criteria:
1. Male or non-pregnant, non-lactating females with an age of greater than or equal to
18 years.
2. The suspected culprit on exchangeable CVC is tunnel ( including implanted ports) or
non-tunneled catheter, antibiotic or non-antibiotic coated catheter inserted in the
subclavian, jugular or femoral vein.
3. Patients must have at least two signs of sepsis from the list below, in any
combination, within 48 hours prior to Daptomycin therapy and no other source for the
bacteremia other than CVC: (a) Core temperature =/>38.0 degrees C or =/<36.0 degrees
C, measured orally, rectally, tympanically or via a central catheter. If axillary add
0.5 degrees C to the measured temperature; (b) Pulse rate =/> 100 beats/min.; (c)
Respiratory rate =/> 20/min; (d) WBC count =/>12,000/mm^3 or =/<4,000/mm^3
differential count showing >10% band forms; (e) Systolic blood pressure=/ <90 mm Hg
4. Patients with suspected or definite diagnosis of uncomplicated CVC-related
gram-positive bacteremia that includes at least one positive blood culture for S
aureus. (If the positive blood culture is drawn through the CVC, then at least >15
colonies/ml will be required or the differential time of positive ( DTP) of CVC at
least 2 hours earlier than the peripheral culture)
5. Signed informed consent
6. No apparent source for the clinical manifestation of bacteremia other than the
catheter
Exclusion Criteria:
1. Creatinine clearance <30 mL/min at the time gram positive bacteremia was diagnosed
unless the patient is on dialysis
2. Bilirubin >4x the upper limit of normal at the time gram positive bacteremia was
diagnosed
3. Treatment with an antibiotic effective against Gram-positive bacterial infections for
more than 48 hours within 72 hours of study medication initiation, unless treatment
failed.
4. Documented S. aureus bacteremia within last 3 months due to source other than CVC.
5. Patients who have participated in another investigational anti-infective study within
30 days
6. History of hypersensitivity to lipopeptides
7. Presence of additional source of infection with same organism cultured from blood,
eg. endocarditis (as evidenced by vegetations on an echocardiogram), septic
thrombosis
8. Conditions with markedly decreased albumin in plasma (<1.5 g/dl), e.g., cirrhosis,
nephritic syndrome, end-stage renal disease
9. Anticipated prolonged therapy >4 weeks
10. Prosthetic endovascular material
11. Oliguria defined as urine output of <20 cc/hour averaged over 24 hours.
12. Possible complicated CRBSI with persistent bacteremia for more than 48 hours on
active antimicrobial therapy (such as osteomyelitis, endocarditis, and septic
thrombosis.)
13. Evidence of catheter site purulence as evidenced by purulent discharge.
14. Patients with diagnosis of pneumonia that is related to S. aureus organism
15. Patients taking concomitant "statins" (HMG-CoA reductase inhibitors)
16. CPK >10X max-normal in asymptomatic patients and CPK >5 max-normal in symptomatic
patients.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Clinical Response Rate
Outcome Description:
Clinical response of Daptomycin administered for treatment of catheter-related bloodstream infections due to S. aureus bacteria, evaluated within 7 weeks of initiating Daptomycin therapy.
Outcome Time Frame:
7 weeks
Safety Issue:
No
Principal Investigator
Issam Raad, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
2005-0622
NCT ID:
NCT00507247
Start Date:
May 2006
Completion Date:
Related Keywords:
- Staphylococcus Aureus
- Catheter-Related Infection
- Bloodstream Infections
- Staphylococcus Aureus
- Daptomycin
- Staphylococcal Infections
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
