Evidence-Based Nursing Worksheet

Randomized Clinical Trials

Appraiser: Madalyn, Gurveen, Julia and Mahnuma

Citation: Kamachi, H., Homma, S., Kawamura, H., Yoshida, T., Ohno, Y., Ichikawa, N., Yokota,
R., Funakoshi, T., Maeda, Y., Takahashi, N., Amano, T., & Taketomi, A. (2020). Intermittent
pneumatic compression versus additional prophylaxis with enoxaparin for prevention of venous
thromboembolism after laparoscopic surgery for gastric and colorectal malignancies: multicentre
randomized clinical trial. BJS Open, 4(5), 804–810. https://doi.org/10.1002/bjs5.50323

Study Question (PICOT): In an adult population on an acute hospital unit between 40-80 years
old how does the use of compression devices with prophylactic anticoagulants (enoxaparin)
compared with just prophylactic anticoagulants (enoxaparin) affect the incidence of deep vein
thrombosis during their hospital stay?

1. Are the results valid?

a. Were the subjects randomly assigned to the experimental and control groups?
i. Yes, the subjects were randomized after registration with a central computer-
generated randomization which was performed by the research coordinators at
the Hokkaido University Hospital’s Clinical Research and Medical Innovation
Centre.
b. Was random assignment concealed from the individuals who were first enrolling
subjects into the study?
i. The article does not specifically state that random assignment was concealed
from the individuals who were first enrolling subjects in the study. The article
states that physicians were designated at each hospital to register subjects
prior to allocation and that allocation into each group one day prior to their
surgery, but does not specify how they were informed about allocation.
c. Were the subjects and providers blind to the study group?
i. No, the subjects were not blind to the study as it was considered impossible to
blind this study due to the interventions being studied. However, the
radiologist who was in charge of the computerized tomography (CT) scan for
the diagnosis of deep vein thrombosis (DVT) was blinded to the subject’s
allocation.
d. Were reasons given to explain why subjects did not complete the study?
i. Yes, after assessing for eligibility seven subjects were excluded as they did
not meet the inclusion criteria. After randomization, 223 subjects were
allocated to the intermittent pneumatic compression (IPC) group, 14 of which
were excluded, leading to 209 entering into the study in this group. 225
subjects were allocated to the PIC and enoxaparin group, and 23 were
excluded, resulting in 202 subjects entering the study. At this stage the reason
for exclusions included, subjects not treated, DVTs detected, anticoagulant
agent added, peritoneal dissemination, haemoglobin level below 9.5 g/dl,
alanine or aspartate aminotransferase more than 2.5 the normal value, total
bilirubin concentration above 3.0 mg/dl, oxygen saturation below 90%, acute
renal failure, CV catheter insertion, postoperative data abnormality, informed
consent withdrawn, conversion to open surgery and incomplete haemostasis.
During the analysis of data one subject was excluded from the IPC alone
group as the CT scan was not completed, and 20 subjects were excluded from
the IPC and enoxaparin group for the CT scan not being completed, pancreatic
fistula, allergy and adverse effects including bleeding and leakage. Bleeding
occurred in 11 of 202 patients in the IPC with enoxaparin group, and one patient
needed a transfusion. All bleeding events were managed by discontinuation of
the drug.
e. Were the follow-up assessments conducted long enough to fully study the effects of
the intervention?
i. Yes, follow up took place seven days post operation and involved a CT scan.
Additionally, follow up for a symptomatic VTE was for 30 days post surgery.
f. Were the subjects analyzed in the group to which they were randomly assigned?
i. All subjects that were not excluded during or after the study were analyzed in
the group they were randomly assigned to. However, all the subjects who had
complications or were excluded for a myriad of reasons were not evaluated
and not included in statistical analysis which could influence statistical
significance.
g. Was the control group appropriate?
i. Yes, the control group received IPC treatment without enoxaparin to
compare the benefits of using enoxaparin alongside IPC. Stratification
factors included sex, location of cancer, age, and institution.
h. Were the instruments used to measure the outcomes valid and reliable?
i. Yes, the instrument used detect the primary outcome of a venous
thromboembolism (DVT and pulmonary embolism) was a multidetector
CT scan which was implemented by a radiologist. Multidetector CT scan
has a high diagnostic accuracy for VTE with a sensitivity of 90% and a
specificity of 95% for PE, and a sensitivity of 97% and a specificity of
100% for DVT diagnosis.
 i. Were the subjects in each of the groups similar on demographic and baseline clinical
variables?
i. Yes, table 1 (Patient demographics and clinical details of randomized and
treated patients) shows the comparison of the two groups for age, sex, location
of cancer, body mass index, and cancer stage. This demonstrates that
similarities between control and intervention groups. The study states that the
subject demographics and clinical characteristics were comparable and that
the surgical characteristics of each group showed no statistical differences.
2. What are the results?
a. How large is the intervention or treatment effect (NNT, NNH, effect size, level of
significance)?
i. Within the IPC group of 208, 10 subjects had a VTE. This was 4.8 % with a
95% confidence interval. Within the IPC with enoxaparin group of 182
subjects, six had a VTE event. This is 3.3% with a 95% confidence interval.
The p value was 0.453 for overall VTE events. In this study a P value less
than 0.050 was considered to be statistically significant
ii. The NNT is 92. Which means that 92 subjects would need to be treated with
enoxaparin and IPC, instead of just IPC, to prevent one additional bad
outcome, being a VTE.
iii. The NNH is -18 meaning the control group (IPC) has a lower risk of the
adverse event of bleeding compared to the intervention group (IPC and
enoxaparin).
b. How precise was the estimation of the intervention effect?
i. The confidence interval was 95%.
3. Will the results help me in caring for my patients?
a. Were all clinically important outcomes measured?
i. Yes, overall VTE events were measured, as well as distal DVT considered to
be below the knee and within the calf veins, proximal DVT that were located
in the popliteal, femoral or iliac veins, PE as well as proximal DVT or PE.
Additionally, bleeding complications were measured, which is important to
consider as it is a common adverse effect of anticoagulant treatment, as well
as surgical site infection and anastomotic leakage.
b. What are the risks and benefits of the treatment?
i. This study found no statistically significant benefit between the control (IPC)
and intervention group (IPC and enoxaparin) in reducing the risk of VTE
events. The risks associated with enoxaparin administration were bleeding
complications. Within the control (IPC) group, which consisted of 208
subjects, not subjects had bleeding complications. Within the intervention
group (IPC and enoxaparin) 11 of 202 subjects reported bleeding
complications, 5.4%. This was further investigated to be ten subjects with
 minor bleeding and one subject with major bleeding. All bleeding events were
managed by discontinuation of the drug.
Additionally, there were not other adverse events in the control (IPC) group,
but the intervention group (IPC and enoxaparin) had five surgical site
infections and five anastomotic leaks.
c. Is the treatment feasible in my clinical setting?
i. Yes, both the administration of enoxaparin and the use of intermittent
pneumatic compression (IPC) are feasible in our clinical setting as both are
interventions that are used separately to prevent VTE events within our
clinical population this term. They are generally affordable interventions that
can be easily implemented with once daily single dose syringes of enoxaparin.
d. What are my patients’/family’s values and expectations for the outcome that is trying
to be prevented and the treatment itself?
i. My client and their family’s values and expectations are that they will not
experience a VTE event while in the hospital, as this will extend their stay and
can lead to serious complications. My client’s and their family’s expectations
are that their prophylactic treatment for the prevention of VTE events will be
implemented based on the best evidence, and with consideration of the risks
and benefits for their specific situation and health history. Treatment should
be given through informed consent and education prior to administration.
Additionally, they expect to be educated about these risks and benefits and to
have their opinions included in their care decisions.

4. Bottom Line: What does this study say about the answer to my PICOT question?
a. In relation to our PICOT question this study determined that there was no statistically
significant difference between the incidence of VTE events between IPC alone and
IPC in parallel with enoxaparin administration in this adult population for the
prevention of VTE events. This study brought forward the importance of considering
the risk and benefits to the use of pharmacological anticoagulants for each specific
client and the corresponding adverse events. Our PICOT is focused on what
prophylactic intervention, or combination of interventions, is most effective for
preventing VTE events, and this study was unable to show a statistical difference in
the rate of VTE events that would allow us to answer our question with one treatment,
or combination of treatments, being more affective than another.

Additional Comments: