Primary objectiveThe primary objective of this trial is to compare TauroSept® (taurolidine 2% solution) with saline solution 0.9% as catheter lock solutions to prevent catheter-related bloodstream infections (CRBSI) in patients on home parenteral…
ID
Source
Brief title
Condition
- Other condition
- Bacterial infectious disorders
Synonym
Health condition
intestinal failure, home parenteral nutrition
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint
Mean number of CRBSI/1*000 catheter days
(Note: Patients without infection after 1 year will have a value of 0.)
Secondary outcome
Secondary endpoints
1. Median time to CRBSI
2. Number and frequency of catheter removals due to catheter-related infections
3. Median time to catheter removal due to catheter-related infections
4. Number and frequency of exit site infections
5. Number and frequency of catheter occlusions
6. Patient satisfaction with the assigned catheter lock solution
7. Costs of catheter lock solution plus costs of hospitalizations, unscheduled
outpatient-clinic consultations, drug treatment costs of infections and
catheter changes
8. Number and frequency of patients having serious adverse events and adverse
events
Background summary
The most recent guideline by the European Society for Nutrition and Metabolism
(ESPEN) states that CRBSI are the most frequent complication of HPN treatment
and that it remains unclear what the optimal agent is to lock catheters and
prevent infections (Staun 2009). While bacteria in the catheter biofilm are
considered to be the major source of CRBSI (Allon 2008), there is evidence
suggesting that heparin, a heterogeneous glycosaminoglycan that is most
commonly used as catheter lock, promotes the formation of bacterial biofilm.
(Shanks 2005). Since antibiotics are less successful than hoped for as
catheter locking solution and because the associated risk for the development
of bacterial resistance, alternatives are urgently needed. While saline
solution 0.9% is increasingly being used as catheter lock as alternative for
heparin, well-powered studies comparing both catheter locking solutions are
eagerly awaited.
A recent single-centre open-label trial (Bisseling 2010) on 14 controls
(heparin) and 16 cases (taurolidine 2% ) showed a dramatic (> 90%) decrease in
recurrence of catheter-related bloodstream infections (CRBSI) in HPN patients
who presented with a proven episode of CRBSI and who continued HPN using either
taurolidine 2% (TauroSept®) or low-dose heparin (150 IU/ml) as a catheter lock.
After crossing over patients of patients who developed CRBSI while on heparin
to taurolidine, none of these patients developed another episode of CRBSI. Also
important, there were no catheter occlusions in either group. However,
limitations of this trial were the open design and the small sample size.
At this point, data from a larger double-blind randomized multi-centre trial in
patients with old and new CVAD are needed to confirm the efficacy of
taurolidine 2% in the prevention of CRBSI in HPN patients with CVADs. Moreover,
a comparison of taurolidine 2% with saline solution 0.9% instead of heparin
should be made because of reasons outlined above.
Study objective
Primary objective
The primary objective of this trial is to compare TauroSept® (taurolidine 2%
solution) with saline solution 0.9% as catheter lock solutions to prevent
catheter-related bloodstream infections (CRBSI) in patients on home parenteral
nutrition (HPN).
Secondary objectives
Secondary objectives are to compare the two devices with respect to further
efficacy parameters, treatment costs and resource utilization, patient-rated
willingness to continue treatment, tolerability and safety.
Primary hypothesis
The primary working hypothesis states that the TauroSept® treatment arm differs
from the saline solution 0.9% treatment arm with respect to the mean number of
CRBSI/1*000 catheter days.
Secondary hypothesis
The secondary working hypotheses state that the TauroSept® treatment arm
differs in further efficacy parameters (e.g. median time to CRBSI, number and
frequency of catheter removals due to catheter-related infections, number and
frequency of exit site infections, number and frequency of catheter occlusions
etc.).
Study design
This is a double-blind, randomized multi-centre controlled trial investigating
the efficacy of TauroSept® and saline solution 0.9% as catheter lock solutions
on the prevention of CRBSI in HPN patients.
Patients will be stratified in two groups according to their risk of developing
CRBSI prior to randomization. Patients receiving a new single lumen central
vascular access device for HPN (new patient starting HPN or patient already on
HPN) will be allocated to the new catheter group (Group I). These patients
therefore have a catheter without any biofim when they enter the trial.
Patient who are already on HPN for at least 1 year prior to trial inclusion who
had a CRBSI rate (bacterial and/or yeast infections) of >0.3/year and have a
catheter in place for at least 6 months will be allocated to the high risk
group (Group II). These patients therefore have a catheter where biofilm
formation may have occurred
Groups I and II will separately be randomized to the two treatment arms
(TauroSept® or saline solution 0.9%).
Intervention
After randomisation the patient wil draw the catheter lock solution (containing
TauroSept® or physiological saline 0,9%) from a blinded vial and fill the
catheter in between TPN administrations and if possible withdraw the catheter
lock siolution before the next use of the catheter.
The content of the blinded vial will be instilled in the catheter by the
patient or his/her caregiver. All patients will receive instructions and will
be trained how to do this in accordance will local treatment protocols of the
participating clinics
Instructions for use:
• Flush the catheter with 10 ml sterile saline 0,9% before instillation of the
catheter lock from the blinded vial
• Draw the catheter lock from the blinded vial and fill the lumen of the
catheter
• Withdraw the catheter locking solution from the catheter and discard this
before use of the catheter for a new infusion
Study burden and risks
The burden and risks associated with participation in this trial are limited to:
- the extension of a regular outpatient clinic visit by 30 minutes to receive
instructions on the instillation and withdrawing of the catheter locking
solution, instructions on storing of the catheter lock vials and the
instruction on how to report any side effects.
- as mentioned in section E9 there is a theoretical risk associated in the form
of allergic or immunogenic reactions to the device or its components
Philips van Leydenlaan 15
6525 EX Nijmegen
NL
Philips van Leydenlaan 15
6525 EX Nijmegen
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria:
1. Benign underlying disease leading to long-term intestinal failure who will receive HPN and/or fluids (saline and/or glucose) at least 2 times /week over a subcutaneously tunnelled single-lumen central venous catheter (Hickman/Broviac or subcutaneous port) for at least one year ;2. a) Patient receives a new single lumen central vascular access device for HPN (new patient starting HPN or patient already on HPN) [allocation to Group I = new catheter group]
or
b) Patient is already on HPN for >=1 year prior to trial inclusion and has a CRBSI rate (bacterial and/or yeast infections) of >0.3/year and a catheter that has been in place for >=6 months (allocation to Group II = high risk group).
(Previous salvage of this catheter by line-lock antibiotics or other therapeutic interventions is not an exclusion criterion as long as this has been performed at least two months before enrolment in the trial)
3. Estimated life expectancy >=1 year
4. Male or female patient aged 18 - 80 years
5. Patient is fully able to understand the nature of the proposed intervention and gives written informed consent before entering the trial.
Exclusion criteria
Exclusion criteria:
Patient who:
1. cannot be expected to comply with the trial plan (substance abuse, mental condition)
2. has significant cardiovascular disease such as unstable angina, acute myocardial infarction or recent cerebral vascular accident (within 6 weeks); a cardiac rhythm which in the investigators judgment may result in significant hemodynamic effects
3. has a known hypersensitivity/allergy to taurolidine 2% or saline solution 0.9%
4. is pregnant, lactating, or nursing.
5. has a current bloodstream infection
6. has any clinically significant abnormalities in PT or PTT requiring intervention
7. has received thrombolytic therapy in the 6 weeks prior to insertion (aspirin 80-325 mg daily is acceptable).
8. has received an investigational drug within 30 days of trial entry
9. has an antibiotic coated, silver impregnated or antimicrobial cuff catheter
10. has compromised skin integrity, including any infection at the insertion site
11. has received parenteral or oral antibiotic therapy < 2 months prior trial inclusion
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL40910.091.12 |