Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02563041 |
| Other study ID # |
UCPel |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
September 23, 2015 |
| Last updated |
September 25, 2015 |
| Start date |
July 2012 |
| Est. completion date |
July 2014 |
Study information
| Verified date |
September 2015 |
| Source |
Catholic University of Pelotas |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Brazil: Ethics Committee |
| Study type |
Interventional
|
Clinical Trial Summary
BACKGROUND: Central venous catheters (CVC) are the only option when hemodialysis is needed
for patients without definitive vascular access. However, CVC use is associated with
complications such as infection, thrombosis, and dysfunction, leading to higher mortality
and expenditures. The aim of this study was to compare the effectiveness of 30% trisodium
citrate (TSC30%) with heparin as CVC lock solution in preventing catheter-related
bloodstream infections (CRBSI) and dysfunction in hemodialysis patients. METHODS:
Randomized, double-blind controlled trial comparing the event-free survival of non-tunneled
CVC locked with heparin or TSC30% in adult hemodialysis patients.
Description:
METHODS Study Design This double blind randomized controlled trial (RCT) was conducted from
July 2012 until July 2014 in the dialysis and transplantation unit of a Brazilian university
hospital. The patients were randomly assigned to have their catheter locked with either
unfractionated sodium heparin 5000 U/mL or 30% trisodium citrate. The randomization was
performed through a computer-generated list of random numbers in blocks of six. Patients and
investigators were unaware of the treatment assignments. Allocation concealment was
performed using opaque, sealed envelopes for assignment.
After each hemodialysis (HD) session, patients assigned to 30%TSC had their catheter lumens
flushed with 0.9% sodium chloride and locked with a volume of 30% TSC solution equivalent to
the catheter internal lumen. Patients assigned to heparin had their catheter lumens flushed
with 0.9% sodium chloride and locked with a volume of 5000 U/mL heparin equivalent to CVC
internal lumen. Catheter care was according to international guidelines, including strict
asepsis on insertion and exit-site dressing changes after each HD session by staff wearing
masks and sterile gloves.
SELECTION OF PATIENTS Patients were eligible for enrollment in the RCT when they were older
than 18 years and had chronic or acute renal failure that required hemodialysis through a
catheter. Patients admitted to the intensive care ward, receiving a tunneled catheter, with
suspected heparin-induced thrombocytopenia, allergy to heparin or TSC30%, with systemic or
localized infection or pregnant women were excluded. The site of insertion and specific type
of catheter were decided by the interventionist physician.
MAIN OUTCOMES Catheter related bloodstream infection (CRBSI): CRBSI was defined as fever
and/or chills during a dialysis session and at least one positive blood culture, with no
other obvious cause of infection after careful clinical examination. The management of the
CRBSI was performed according to guidelines. Empirical antibiotic therapy was immediately
given. The catheter was removed if there was isolation of S. aureus or fungus, or there was
no clinical recovery within 48 hours of antibiotic treatment.
Catheter dysfunction: Dysfunction was defined as a persistent inability to obtain a blood
flow above 200 mL/min. In this situation, the catheter was removed or exchanged over
guidewire.
OTHER PREDICTORS Patients-related: Data was also collected about age, gender, skin color,
presence of diabetes, diagnosis of CKD or acute kidney injury, and hemodialysis vintage.
Catheter-related: Site of insertion (jugular, subclavian or femoral vein), and ordinal
number of catheter in the same patient (considering only the study period).
STATISTICAL ANALYSIS Calculation of the required sample size was based on main outcomes. It
was assumed that the group with heparin lock would have a rate of catheter-related
bloodstream infection of 150% greater than that of catheters with TCS30% lock. With a
two-sided test, and an alfa error of 5% and 80% of power, it was required 112 catheters for
each group.
The primary analysis was made through survival analysis with Cox proportional hazard
regression. Initially the investigators proceed to univariate analysis using Kaplan-Meier
curves and log rank test for the categorical variables, and univariate Cox regression for
continuous variables. The predictors which have a p-value lower than 0.25 in univariate
analysis were included in final model. Interactions were checked for any possible
association of predictors. The likelihood ratio test was used for compare nested with full
models. The proportionality of predictors was verified by introduction of time-dependent
variables in the model. If any predictor violates the proportionality assumption, the
analysis would be stratified for that predictor. Well-functioning catheters at the end of
the study period, catheters removed because patients acquired functional arteriovenous
fistula, renal function recovery, changed to peritoneal dialysis or had transplantation were
analyzed as censored data. The analysis was all done on intention-to-treat base. All
reported p-value are two sided. The analysis was performed using the STATA 11.2 statistical
software (Stata Corporation, College Station, TX, USA)
ETHICAL ASPECTS The study protocol was approved by the local review board. Written informed
consent was obtained from all patients before enrollment.
