Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00300092 |
| Other study ID # |
CCI 99.156 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
March 6, 2006 |
| Last updated |
April 16, 2015 |
| Start date |
September 2000 |
| Est. completion date |
July 2004 |
Study information
| Verified date |
April 2015 |
| Source |
Children's Hospital Los Angeles |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Institutional Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
Study objective: Fingertip injuries are common in the pediatric population. Considerable
controversy exists about whether prophylactic antibiotics are necessary after repair of such
injuries. Our goals were to estimate the rate of bacterial infection among pediatric
patients with distal fingertip injuries overall and to compare the rate of bacterial
infections among subgroups treated with and without prophylactic antibiotics.
Methods: This was prospective randomized control study of pediatric patients presenting to
an urban children's hospital with trauma to the distal fingertip requiring repair. Patients
were randomized to two groups: those receiving prophylactic antibiotics (Cephalexin) and
those who did not receive antibiotic therapy. Repairs were performed in a standardized
fashion and all patients were re-evaluated in the same emergency department in 48 hours and
by phone 7 days later. The primary outcome of this study was the incidence of infection.
Description:
MATERIAL and METHODS Study design, Setting and Selection of Participants
This prospective randomized control trial was conducted at an urban children's hospital
Emergency Department with 56,000 visits annually. The Institutional Review Board (IRB)
approved the study prior to subject enrollment. The study period was from September 2000 to
July 2004. All patients under 18 years of age presenting to the Emergency Department with a
fingertip injury distal to the distal interphalangeal joint were eligible to participate.
Patients were excluded from the study if the time from injury to repair was greater than
eight hours, if the patients had diabetes, an oncologic disorder, an immune deficiency, a
bleeding disorder, used steroids regularly, presented with a grossly contaminated wound,
were currently taking antibiotics, or had a previous allergic reaction to cephalosporins.
The study was formulated as an equivalence trial to demonstrate non-inferiority of repair
without versus with prophylactic antibiotics. The rate of infection 7 days after repair was
the primary outcome variable. Determination of the target sample size was based on a
combination of practicality and maximum difference between infection rates consistent with
equivalence. It was judged feasible to enroll 160 subjects over the course of the study.
Sample sizes of 80 per group would have 80% power to conclude with 95% certainty that the
infection rates in the two groups were equivalent. This calculation is based on an upper
1-sided 95% confidence limit for the difference in infection rates, with percent infected of
6.25% in both groups, and the maximum allowable difference resulting in equivalence to be
10.6%.
Intervention
All wounds were treated following a standardized protocol.9, 10 First, the degree of injury
was recorded. Fingertips were classified into one of five categories: no laceration (damage
to nailbed), simple laceration, loss of skin or pulp, partial amputation or complete
amputation. Subungal hematomas were drained by cautery. Hand x-rays were obtained to detect
fractures, dislocations, or foreign bodies. Lacerations were irrigated with 500cc normal
saline after a digital block with 1% lidocaine (no epinephrine). Devitalized tissue was
removed. Skin lacerations and nail bed injuries were repaired with chromic gut. Xeroform
gauze was then applied to the repaired finger and a bulky dressing secured. A tetanus
booster was given if patient's immunizations were not up-to-date. At discharge study
participants were given a standard wound care instruction sheet and a scheduled follow-up
appointment at 48 hours. Subjects were told to return immediately to the same Emergency
Department if they noticed signs or symptoms of infection, including the presence of
redness, warmth, tenderness, swelling, discharge or fever.
All wounds were repaired by residents, fellows, and/or attending physicians in the Emergency
Department. In-service training was provided in the Emergency Department prior to starting
the study and periodically during the study period to assure consistency in the repair
process. If the wound was repaired by a resident or fellow, the attending in the Emergency
Department provided direct supervision.
After standard wound repair, eligible patients (and caregivers) were approached for
enrollment. Interpreters were provided if the caregiver's or patient's primary language was
not English. If caregivers and appropriate study subjects agreed, informed consent was
obtained. Participants were then randomized to one of two groups using a randomization list
prepared in advance with PROC PLAN within the Statistical Analysis System (SAS).11 Subjects
assigned to Group 1 received no antibiotics after fingertip repair. Group 2 received
prophylactic antibiotics (Cephalexin 50 mg/kg three times daily), upon discharge for 7 days.
Cephalexin was chosen as the antibiotic of choice because the majority of wound infections
are caused by gram positive organism (Staphylococcus and Streptococcus species). The full
7-day course of antibiotics was dispensed to study subjects prior to discharge. The cost of
the antibiotics was covered by the General Clinical Research Center (GCRC).
A 48-hour follow-up visit was scheduled and the subject was told that one of the primary
investigators would contact them by phone in 7 days. Subjects received instructions to keep
their hand elevated, to keep the dressing clean and dry, to leave the dressings in place and
to return to the Emergency Department immediately if signs or symptoms of wound infection
developed.
At the follow-up visit and with the phone call, one of the three study investigators
evaluated for the presence of infection, compliance with antibiotics, and wound healing.
Infection was determined by the presence of erythema, tenderness, warmth, purulent
discharge, regional lymphadenopathy, and fever. Subject compliance with the antibiotic
regime was recorded at 48 hours and at 7 days after repair. Compliance was determined by
phone follow-up asking the caregiver to measure the amount of antibiotic left in the bottle
and asking for the number of doses administered.
Data Collection and Processing
Study data were collected at the initial visit by the physician repairing the wound. Data
from the 48 hour and 7 day phone follow-up were collected by one of the three primary
investigators. All data was recorded on a standardized data collection form and then entered
into a computerized Microsoft Excel spreadsheet. All hospital charts were reviewed by the
primary investigator at the close of the study for quality assurance purposes.
Statistical Methods
The two groups were compared for age, gender, time of injury, place of injury, mechanism of
injury, finger involved, presence of fracture, complexity of injury, level of training of
the treating physician, laceration experience of the treating physician, and number of
sutures placed, using the 2-sample t-test or the Wilcoxon rank sum test for continuous
variables and Fisher's exact test or a Chi squared test for categorical variables. The rate
of infection 7 days after repair was calculated for each treatment group, along with exact
binomial 95% confidence intervals. To assess the equivalence of the two treatments, the
difference D = infection rate in the No Antibiotic Group minus infection rate in the
Antibiotic Group was calculated. The upper limit of a 1-sided 95% confidence interval for D
was used to estimate the maximum amount by which the infection rate without antibiotics may
exceed that with prophylactic antibiotics. Additional analyses included comparison between
dropouts and those who completed the study on demographic variables and wound and repair
characteristics, and comparisons between those with and without infection to identify
potential predictors of infection other than group assignment. NCSS 2004 software was used
for equivalence testing.12 Statistical tests comparing group characteristics were 2-sided
and considered significant for p<0.05, using the SAS software, version 8.11
DATA ANALYSIS
Characteristics of Study Subjects
A total of 146 subjects were initially enrolled in the study. The study was terminated
earlier than expected because of staffing issues. Eleven participants were withdrawn prior
to study completion. Those not completing the study included four subjects who could not be
reached for phone follow-up, three subjects who received antibiotics during the study period
for a reason other than infection of the fingertip, two subjects for whom insufficient data
was available for analysis, one subject who received antibiotics prior to repair and one
subject who requested to be withdrawn from the study prior to completion. These eleven
subjects were significantly older than those who completed the study (6.0 +/- 3.8 vs. 3.1
+/- 2.7 years, p=0.001), but were similar on all other baseline characteristics. In
addition, subjects were equally distributed between the 2 groups: 6/75 (8%) from Group 1(No
Antibiotic) and 5/71 (7%) from Group 2(Antibiotic) (p=1.0).
A total of 135 subjects completed the study, 69 assigned to Group 1(No Antibiotic) and 66
assigned to Group 2(Antibiotic). Baseline characteristics of the two groups are shown in
Table 1. Values tabulated are mean + s.d. for continuous variables and number and percent
for categorical variables. No statistically significant differences on any baseline values
were found between the two treatment groups. At the 7 day interview, the percent who
reported consuming at least 75% of the prescribed doses was 86.2% (95% CI: 75.3%, 93.5%).
Results
At 7 days after repair, one subject in each treatment group had an infection. The subject in
the No Antibiotic Group was treated with oral antibiotics and the subject in the Antibiotic
Group was treated with intravenous antibiotics. Both made a full recovery. The infection
rate (95% confidence interval) was 1.45% (0.04%, 7.81%) for the No Antibiotic Group and was
1.52% (0.04%, 8.16%) for the Antibiotic Group, not statistically significant (p=1.00). The
upper limit of a 1-sided 95% confidence interval for the difference in rates was 4.9%
indicating that there is a 5% chance that the infection rate in subjects not treated with
antibiotics would exceed that of subjects treated with antibiotics by more than 4.9%.
Although the number of infections was too small for meaningful statistical comparisons,
examination of the two infected cases revealed that the number of sutures was considerably
larger than that among the uninfected subjects. The number of sutures for the two infected
subjects was 8 and 9 (mean=8.5; standard deviation=0.7) and the mean (S.D.) for the
uninfected subjects was 4.9 (2.0). After the completion of the study, chart review revealed
four infections presenting beyond the seven-day window (Days 7-14), three in the Antibiotic
Group and one in the No Antibiotic group. Interestingly, 41% of all wounds involved a
fracture and none of these became infected.
