Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03711981 |
| Other study ID # |
16-027 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 27, 2016 |
| Est. completion date |
December 15, 2017 |
Study information
| Verified date |
May 2018 |
| Source |
University of Tennessee |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
More than 600,000 hysterectomies are performed in the United States each year, making it the
most common non-obstetric major surgery performed on women1. Estimates suggest that at least
30% of hysterectomies are performed laparoscopically or robotically with an increasing trend
toward minimally invasive approaches2. While a minimally invasive approach certainly provides
improved recovery, patients still experience substantial pain and most require opiate
medications for pain control. Incorporating a multimodal approach to postoperative pain
management through the use of field nerve blocks is potentially an ideal way to enhance
recovery and minimize the need for narcotic pain medications.
Over the past decade, the use of Transversus Abdominis Plane (TAP) blocks as an adjunct for
postoperative pain management has gained in popularity. First described in 2001 by Dr. Rafi
of Limerick3, Ireland, TAP blocks are now typically performed by an anesthesiologist with the
use of ultrasound guidance. The transversus abdominis plane is the neurovascular plane
between the aponeurosis of the internal oblique and transversus abdominis muscles. Herein lie
the afferent nociceptor nerve endings of T7-L1. Injection of a 20-30cc volume of anesthetic
into this plane causes a sensory nerve block to the ipsilateral antero-abdominal wall from
the costal margin to the symphysis pubis4.
Clinical trials have documented the validity of using TAP blocks for both open and
laparoscopic procedures and verified their use for postsurgical pain relief. Studies have
demonstrated that TAP blocks for both open and laparoscopic hysterectomies are safe and
efficacious5, 6. In 2011, De Oliveira et al. demonstrated improved quality of recovery for
women undergoing preoperative ultrasound guided TAP infiltration with ropivacaine at the time
of laparoscopic hysterectomy7.
Description:
The primary goal of our study is to demonstrate that laparoscopically assisted bilateral
Transversus Abdominis Plane (TAP) block using liposomal bupivacaine is superior to
pre-incisional injection of bupivacaine in terms of peri-operative opiate use, pain scores
and overall patient satisfaction up to one week following surgery. Our recent research has
already demonstrated the safety of performing Laparoscopic assisted TAP blocks using
liposomal bupivacaine.
This trial will evaluate the efficacy of laparoscopic TAP blocks with liposomal bupivacaine
by using VAS/numeric pain scores at rest and with cough in recovery at 1 and 2 hours post-op.
The trial will also utilize an OBAS patient survey, document peri-operative opioid pain
medication used intraoperatively, in PACU and overnight (if admitted), and assess length of
time in PACU and same-day discharge versus admission. Opioid pain medication use at home up
to one week will also be recorded.
HYPOTHESES/SPECIFIC AIMS The goal of this research project is to prove that a
laparoscopically delivered TAP block using a combination of Liposomal bupivacaine (Exparel)
and Bupivacaine is an effective and feasible means for decreasing post-operative pain from
the immediate post-operative period up to one week.
The research aims to demonstrate that TAP blocks, when delivered laparoscopically and by
using Liposomal bupivacaine will show a 20% benefit in post-operative QoR-15 scores on
post-operative days 1,2 and 7. Other objectives of our study will be to evaluate
peri-operative narcotic medication dosing, VAS/Numeric pain scores with cough at 1 and 2
hours in PACU, overnight narcotic use for patients who are admitted and narcotic pain pill
use at home up to 7 days. Finally, the study aims to confirm that this technique is simple to
perform, easy to implement and would offer a multi-modal anesthetic alternative to the
excessive use of post-operative opioid pain medications.
Patients scheduled for laparoscopic or robotic hysterectomy are screened in the
pre-anesthesia care unit and if eligible are invited to enroll in the trial. Primary
Attendings for each surgery will advise patients of the option for the trial at pre-operative
appointments. Patients who agree to enrollment are appropriately consented and then
randomized to either control (pre-incisional anesthetic) or study (TAP) group. The patient
remains blinded to the arm of the study, but OR personnel are advised so as to prepare
medications and syringes.
Following induction of anesthesia, the patients in the TAP block arm are prepared and draped
for surgery allowing for mid-axillary access along the flank bilaterally. Once
pneumoperitoneum and a port for the laparoscope were established, TAP block is performed
bilaterally by first palpating the external landmark within the Triangle of Petit, 2 cm above
the iliac crest. A 21-gauge Stimuplex ® A insulated needle (Braun, Melsungen, Germany) is
used to enter the transversus abdominis neurovascular plane. Bilaterally, TAP block patients
receive 10cc of liposomal bupivacaine combined with 10cc of 0.25% bupivacaine and 10cc normal
saline. Patients in the pre-incisional injection arm of the study receive a total of 20cc of
0.25% bupivacaine total, equally distributed between the incisions. All patients receive
routine general anesthesia with opiate use adjusted as determined by the anesthesia provider.
The anesthesia team is neither blinded nor given specialized protocol instructions. At the
end of each case, narcotic dosage used is documented.
All of the patients will receive phone calls on post-operative days 1,2 and 7. They will be
asked their opiate pain medication usage, number of pills used and "Overall Benefit of
Anesthesia" (OBAS) scores will be obtained. The OBAS is a simple quality assessment
instrument shown to reliably measure benefit from post-operative pain therapy16 (Table 1).
Table 1. Overall Benefit of Analgesia Score
1. Please rate your current pain at rest on a scale between 0=minimal pain and 10=maximum
imaginable pain
2. Please grade any distress and bother from vomiting in the past 24 h (0=not at all to
10=very much)
3. Please grade any distress and bother from itching in the past 24 h (0=not at all to
10=very much)
4. Please grade any distress and bother from sweating in the past 24 h (0=not at all to
10=very much)
5. Please grade any distress and bother from freezing in the past 24 h (0=not at all to
10=very much)
6. Please grade any distress and bother from dizziness in the past 24 h (0=not at all to
10=very much)
7. How satisfied are you with your pain treatment during the past 24 h (0=not at all to 10=
very much)
OBJECTIVES The primary goal of our study is to demonstrate that laparoscopically
assisted bilateral Transversus Abdominis Plane (TAP) block using liposomal bupivacaine
is superior to pre-incisional injection of bupivacaine in terms of peri-operative opiate
use, pain scores and overall patient satisfaction up to one week following surgery. Our
recent research has already demonstrated the safety of performing Laparoscopic assisted
TAP blocks using liposomal bupivacaine.
This trial will evaluate the efficacy of laparoscopic TAP blocks with liposomal
bupivacaine by using VAS/numeric pain scores at rest and with cough in recovery at 1 and
2 hours post-op. The trial will also utilize an OBAS patient survey, document
peri-operative opioid pain medication used intraoperatively, in PACU and overnight (if
admitted), and assess length of time in PACU and same-day discharge versus admission.
Opioid pain medication use at home up to one week will also be recorded.
HYPOTHESES/SPECIFIC AIMS The goal of this research project is to prove that a
laparoscopically delivered TAP block using a combination of Liposomal bupivacaine
(Exparel) and Bupivacaine is an effective and feasible means for decreasing
post-operative pain from the immediate post-operative period up to one week.
The research aims to demonstrate that TAP blocks, when delivered laparoscopically and by
using Liposomal bupivacaine will show a 20% benefit in post-operative QoR-15 scores on
post-operative days 1,2 and 7. Other objectives of our study will be to evaluate
peri-operative narcotic medication dosing, VAS/Numeric pain scores with cough at 1 and 2
hours in PACU, overnight narcotic use for patients who are admitted and narcotic pain
pill use at home up to 7 days. Finally, the study aims to confirm that this technique is
simple to perform, easy to implement and would offer a multi-modal anesthetic
alternative to the excessive use of post-operative opioid pain medications.
PRELIMINARY WORK IRB protocol #14-132 was discontinued 12/14/15 due to a protocol
violation. Because the study could not be completed with its original objectives, we are
seeking to repeat the study with a very similar protocol. While talking with patients
during the audit of their post-operative phone calls, it became clear that the
experimental arm of the study might, in fact, have had a beneficial impact on
post-operative recovery. As we do not have that portion of the data, we are seeking to
repeat the study with a few minor modifications.
METHODS
1. Study Design Proposed study design is for a Prospective Single blinded Randomized
Clinical Trial. The study aims to evaluate two arms and compare them: All patients
would undergo laparoscopic total hysterectomy or Robotic assisted laparoscopic
total hysterectomy with or without removal of adnexa. Patients would not be
excluded for having other simultaneous procedures such as appendectomy, excision of
endometriosis or pelvic lymph node dissection. Patients in one arm of the study
would receive a bilateral Laparoscopic Assisted TAP block with 10cc Liposomal
bupivacaine, 10cc 0.25% bupivacaine and 10cc normal saline each bilaterally at the
beginning of their surgery. The patients in the control arm of the study would
receive pre-incisional injections at the trocar incision sites using a total of
20cc 0.25% bupivacaine.
2. Study Subjects
1. Women undergoing laparoscopic hysterectomy or robotic assisted laparoscopic
hysterectomy with or without removal of adnexa would be eligible. Patients will be
randomized.
2. Inclusion Criteria: Women undergoing TLH at Erlanger Hospital. They must be 18
years or older due to restrictions on Exparel. Women undergoing simultaneous lymph
node dissection, appendectomy, adhesiolysis or other incidental procedures would
not be excluded.
3. Exclusion Criteria: Patient refusal. Soft tissue infection of the abdominal wall
and skin. Abnormality at the needle insertion site. Chronic opiate use within 3
months prior to surgery. Age less than 18 years. Anticipated need for extension of
incision greater than 2cm. Hepatic or renal impairment, current pregnancy or BMI
>50.
c. Sample Size: 100 patients, 50 in each arm of the study. The sample size calculation
is based on an assumption that a 24% difference in VAS pain scores would be clinically
meaningful. A sample size of 41 patients in each cohort would be able to detect a 20%
difference in post-operative QoR-15 quality of life post-surgery scores with a power of
80%. This calculation was done with the assistance of Jenny Holcomb, PhD (See
accompanying paperwork).
d. Data Collection: Each patient will have paperwork designating name, demographics,
telephone numbers as well as pertinent PHI. Documentation of VAS scores, time-frame to
first request for opiate pain medications, post-operative pill counts and follow-up
phone questionnaire (OBAS) will be collected on accompanying forms.
e. Data Handling: A file, with the paper work on each patient, will be handled by the
Principal Investigator, Shanti Mohling, MD and primary Co-investigator, Rayan Elkattah,
MD. Two personnel will be recruited to handle post-operative phone calls. They will be
carefully screened for reliability and phone-calls assessments will be periodically
audited to avoid the concerns occurring with #14-132. The charts will be stored in the
primary investigator's private office or in the research specialist's office (Patricia
Bush) during analysis.
f. Data Analysis: Following collection of data and collation of all data, the results
will be statistically analyzed with the help of statistician Jenny Holcomb, PhD.
g. Time Frame:
1. 12 months for data collection. 2. 18 months time for completion of study including
analysis. h. Strengths/Innovation: Adding a simple technique for post-operative pain control
to the armamentarium of multi-modal anesthesia techniques will greatly enhance the options
for caring for patients around the time of laparoscopic surgery. Currently, I believe the
laparoscopic TAP block is a valuable, yet underutilized tool in the field of Minimally
Invasive Surgery.
i. Limitations:
1. Liposomal bupivacaine is a milky white color and it would have been very difficult to
blind the surgeons infiltrating it as opposed to a placebo.
2. There is a learning curve with developing an ability to do the TAP block
laparoscopically, however this technique has now been well practiced by our team.
3. BMI, additional procedures, history of other pain issues, such as fibromyalgia, may all
be confounders to this study. All of these will be documented and hopefully averaged in
the randomization.
VII. RISKS/BENEFITS
1. Risks and side effects related to the TAP Block with liposomal bupivacaine include
bruising at the site of the injections, soreness, and a rare potential for intravascular
injection causing cardiac arrhythmia. These risks are similar to the risk of routine
bupivacaine in the trocar sites routinely used anyway. Of note, there were no
complications of laparoscopic TAP blocks during the course of our recent trial #14-132.
2. There are no known direct benefits to study subjects.
3. If the study demonstrates a benefit of the TAP block in controlling post-operative pain
better than simply using pre-incisional injections and decreases patient need for opiate
analgesia this will undoubtedly benefit patients in future.
4. There are no potential ethical concerns with this study, especially given that it will
be randomized.
BUDGET Primary costs incurred will be files and paper products for VAS scores, charting on
recovery and post-op questionnaires. The cost of the procedural medications will be rolled
into the global surgical charge as pre-incisional anesthetics are already routinely billed
for.
RESEARCH ENVIRONMENT All procedures will all take place at the time of surgery in the
operating room. Patients will receive information on the study in pre-op consultation or at
the time of arrival to the Pre-op arena.
