Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02578745 |
| Other study ID # |
IRB ID # 201508154 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 2015 |
| Est. completion date |
March 2016 |
Study information
| Verified date |
November 2019 |
| Source |
Washington University School of Medicine |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Surgical site infections (SSIs) complicate 5 - 12% of cesareans. Negative pressure wound
therapy (NPWT) - a closed, sealed system that applies negative pressure to the wound surface
- has been used to treat open wounds since the late 1990s. Experimental evidence suggests
NPWT promotes wound healing by removing exudate, approximating the wound edges, and reducing
bacterial contamination. Although effectiveness of prophylactic NPWT is biologically
plausible and non-randomized studies suggest benefit in reducing SSIs, good quality data is
lacking. The objective of this pilot randomized controlled trial of 120 patients to test the
hypothesis that prophylactic NPWT will reduce SSIs and other wound complications after
cesarean in obese women. The investigators will randomly assign obese women undergoing
cesarean delivery to Standard dressing or prophylactic NPWT with the PICO system after skin
closure. The primary outcome will be a composite of superficial or deep SSIs per Centers for
Disease Control and Prevention (CDC) criteria and other wound complications (separation,
hematoma, seroma) after cesarean.
Secondary outcomes will include wound dehiscence (≥2 cm); hematoma; seroma; composite of
wound complications; patient pain and satisfaction scores; physician office visit or
emergency department (ED) visits for SSIs; and hospital readmission for wound complications.
Description:
Overview of the Proposed Trial
This will be a pilot randomized controlled trial. The investigators chose a randomized
controlled trial, the 'gold standard' of clinical research design, with the goal of obtaining
the highest quality evidence to inform clinical practice. Randomly allocating subjects to
different interventions minimizes selection bias and results in groups that are comparable
with regards to important confounding variables, both measured and unmeasured. Additionally,
the broad inclusion criteria, simplicity of the interventions, and evaluation of effects of
typical use of prophylactic NPWT make this a pragmatic trial. The investigators will follow
the Consolidated Standards of Reporting Trials (CONSORT) guidelines in the conduct and
reporting of this trial. We will use computer-generated block randomization stratified by
study site and BMI category to assign participants to the two interventions. All subjects
will receive standard infection prevention measures including skin antisepsis and
weight-adjusted prophylactic antibiotics. Analysis will follow the intention-to-treat
principle. The use of broad inclusion criteria and intention-to-treat analysis will allow a
more conservative estimate of the effect of prophylactic NPWT and allow a better estimate of
effectiveness and public health implications of practice change than would pure estimate of
efficacy alone.
Conduct of the Trial Recruitment of study subjects: All women admitted to the labor and
delivery units of the participating medical centers will be screened against inclusion and
exclusion criteria. Eligible subjects will be approached by trained research staff for
written consent to participate in the study. Subjects will be randomized only when the
decision is made for cesarean delivery.
Randomization and allocation concealment: Enrolled subjects will be randomly assigned in a
1:1 ratio to NPWT or standard care using a computer-generated random sequence generated by
the study statistician. A subject's group assignment will be revealed only after the decision
is made to perform cesarean delivery.
Blinding: Although blinding of both subjects and physicians would be ideal, blinding is not
possible in this trial. We will minimize systematic bias by applying the same standard
infection prevention measures in all patients at each site. Further, the research personnel
collecting outcomes data will be blinded to the group assignments of the subjects after the
standard dressing or NPWT device have been removed. Importantly, diagnosis of the primary
outcome will be objectively reviewed centrally by the PI in a blinded fashion using to CDC
criteria.
Interventions: The interventions to be compared in this trial are standard care versus
prophylactic NPWT after skin closure:
1. Standard care: Women assigned to standard care will receive routine postoperative wound
dressing consisting of layers of gauze and adhesive tap. The dressing will be removed
after 24 - 48 hours.
2. Prophylactic NPWT: Women assigned to prophylactic NPWT will have the PICO device applied
and secured with fixation adhesion strips. The device will be monitored while the
patient is in the hospital to confirm that it is functioning well. The device will be
removed prior to discharge, typically on postoperative day 4.
Rationale for choosing PICO: There are no head-to-head trials of the two FDA-cleared
prophylactic NPWT devices, and the preliminary data do not suggest one is superior to the
other. However, there is a large price difference: $200 per PICO unit and $500 per Prevena
unit. The investigators chose the less expensive device.
Data Collection: The investigators will collect detailed antepartum, intrapartum, and
postpartum information from study participants. Relevant data will be collected initially to
assess eligibility. Complete baseline information and outcome data will be collected by
trained study nurses by direct interview and chart review.
Hypothesis Testing Primary Aim: Determine the effectiveness of prophylactic NPWT in reducing
the rate of SSIs and other wound complications after cesarean in obese women.
Hypothesis: Obese women will have lower rates of SSIs and other wound complications after
cesarean with use of prophylactic NPWT than with standard care.
Primary outcome: The primary outcome for the trial is superficial or deep SSIs and other
wound complications (separation, hematoma, seroma) after cesarean. This will be defined
according to CDC criteria as infections at the surgical site occurring within 30 days of
cesarean delivery, and classified as superficial, deep, or organ/space occupying. We will use
active surveillance for SSIs including one patient phone call by the research coordinator
within 30 days after surgery. The PI will blindly review de-identified inpatient and
outpatient records of all subjects with suspected SSIs against CDC criteria to ensure
standard diagnosis and classification.
Secondary outcomes: Wound dehiscence (≥2 cm); hematoma; seroma; composite of wound
complications; patient pain and satisfaction scores (on a scale of 0 to 10) at discharge and
postoperative day 14 (±2 days) and 28 (±2 days); physician office visit or ED visits for
SSIs; and hospital readmission for SSIs.
Sample size calculation: The sample size for this pilot trial is 120; 60 in the prophylactic
NPWT group and 60 in the standard treatment group. We estimated the sample size for the trial
assuming a baseline SSI and wound complication rate of 24% based on a recent trial at our
institution, and we a clinically significant 75% reduction effect size based on a recently
published study.
CDC Criteria for defining and classifying surgical site infections (SSIs):
1. Superficial incisional (wound) infection infection occurs within 30 days after operative
procedure; AND involves only skin and subcutaneous tissue of the incision; AND patient
has at least one of the following:
1. purulent drainage from the superficial incision,
2. organisms isolated from an aseptically-obtained culture from the superficial
incision or subcutaneous tissue,
3. superficial incision that is deliberately opened by a surgeon, attending physician
or other designee and is culture-positive or not cultured; and patient has at least
one of the following signs or symptoms: pain or tenderness; localized swelling;
erythema; or heat. A culture-negative finding does not meet this criterion,
4. diagnosis of a superficial incisional SSI by the surgeon or attending physician or
other designee.
2. Deep incisional (wound) infection
Infection occurs within 30 days of operative procedure; AND involves deep soft tissues
of the incision (e.g., fascial and muscle layers); AND patient has at least one of the
following:
1. purulent drainage from the deep incision,
2. a deep incision that spontaneously dehisces, or is deliberately opened or aspirated
by a surgeon, attending physician or other designee and is culture-positive or not
cultured; and patient has at least one of the following signs or symptoms: fever
(>38°C), localized pain, or tenderness. A culture-negative finding does not meet
this criterion,
3. an abscess or other evidence of infection involving the deep incision that is
detected on gross anatomical or histopathologic exam, or imaging test.
3. Organ/Space (endometritis, abscess)
Infection occurs within 30 days of operative procedure; AND infection involves any part of
the body deeper than the fascial/muscle layers, that is opened or manipulated during the
operative procedure; AND patient has at least one of the following:
1. purulent drainage from a drain that is placed into the organ/space (e.g., closed suction
drainage system, open drain, T-tube drain, CT-guided drainage),
2. organisms isolated from an aseptically-obtained culture of fluid or tissue in the
organ/space,
3. an abscess or other evidence of infection involving the organ/space that is detected on
gross anatomical or histopathologic exam, or imaging test; AND meets at least one
criterion for a specific organ/space infection site.
Secondary Aim 1: Assess the safety of prophylactic NPWT in obese women as measured by
frequency of adverse events including skin blisters, erythema, wound bleeding and prolonged
wound drainage.
Hypothesis: The rate of adverse events will not be significantly higher with use of
prophylactic NPWT than with standard care.
Outcomes for secondary aim 1: Composite of adverse events potentially attributable to NPWT
including skin blisters, erythema, wound bleeding, and prolonged (>7 days) wound drainage.
Rationale: NPWT has been associated with adverse events including skin blisters, wound
bleeding, and prolonged wound drainage. A high rate of skin blisters was reported when NPWT
was used after orthopedic surgery. This was attributed to use of the adhesive dressing in the
setting of marked swelling and edema. Although the adverse events noted with NPWT after
cesarean have generally been minor and were comparable in frequency to use of standard
dressing, it is essential to characterize the frequency of these events to permit
risk-benefit counseling of patients.
Secondary Aim 2: Determine the effect of prophylactic NPWT on the frequency and identity of
bacteria, including antibiotic-resistant organisms, isolated from SSIs after cesarean in
obese women.
Hypothesis: Prophylactic NPWT will be associated with a reduction in the rate of positive
wound cultures and antibiotic-resistant bacteria isolated from SSIs after cesarean.
Outcomes for secondary aim 2: Rate of positive wound cultures and proportion of specific
organisms, especially drug-resistant bacteria (e.g. MRSA) isolated from SSIs after cesarean.
Wound cultures and antimicrobial sensitivity testing: Physicians will follow clinical
protocols that warrant collection of swabs from all accessible SSIs for routine aerobic and
anaerobic cultures.
Data Analysis Plan Overview: Data analyses will adhere closely to the CONSORT guidelines.
Analyses will follow the intention-to-treat principle in which subjects will be analyzed in
the group to which they were randomized, regardless of whether or not they received the
assigned intervention.
Primary Analysis: Descriptive statistics will characterize the group of individuals recruited
and investigate comparability of the two groups at baseline. Formal statistical testing will
be limited to selected baseline characteristics considered to be prognostic factors for the
primary outcome such as emergent cesarean, type of skin incision, and prolonged rupture of
membranes. The categorical prognostic factors will be compared between trial groups by using
the Fisher's exact test. Continuous prognostic factors will be compared using the
Mann-Whitney U test.
The primary outcome and other categorical secondary outcomes will be compared between
intervention groups by using the Cochran-Mantel-Haenszel test.The investigators will
calculate common relative risks and 95% confidence intervals associated with the primary and
secondary outcomes. The investigators will also conduct time-to-event analyses by using
Kaplan Meier and Cox regression models to examine the pattern of SSIs in the two groups.
Secondary Analyses: The investigators will perform other analyses aimed at obtaining adjusted
estimates of treatment effectiveness, adjusting for baseline subject characteristics
(covariates). The objectives of these analyses are to estimate the influence of covariates on
the outcome and to use covariates to improve the estimated difference between treatment
groups. Stepwise logistic regression models will be used to identify and estimate the effect
of multiple prognostic factors on the probability of SSI and other categorical outcomes.
Interaction tests will be used to determine whether the effectiveness of prophylactic NPWT
differs across these subgroups such as BMI category and type of skin incision. These
secondary analyses will be considered exploratory.
Safety monitoring
The interventions compared in this trial are both currently used in clinical obstetric
practice. Further, the adverse events reported with use of prophylactic NPWT at cesarean were
minor and their frequency was comparable to rates with standard dressing. Therefore, no
serious or life-threatening adverse events are expected. Nonetheless, the following measures
will be taken to monitor and investigate adverse events:
1. Adverse events reporting: Detailed information concerning adverse events will be
collected and evaluated throughout the trial. If a participant develops an adverse
event, the participant's physician and PI will ascertain the safety of continuing the
intervention.
2. Interim analyses: The investigators anticipate one interim analyses after 60 patients
have recruited. Although early stopping decisions cannot be based purely on a
mathematical stopping rule, we will use the Haybittle-Peto stopping rule as a guide.
Under this rule, the interim analyses of the primary outcome would have to demonstrate
an extreme difference between groups (P <0.001) to justify premature disclosure. This
rule has the advantages that the exact number of interim analyses need not be specified
in advance and the overall type I error is preserved at 0.05; therefore, samples size
adjustment is not needed.
