Clinical trial NCT02056301
Conditions: Pectus Excavatum
Sponsor: Baylor College of Medicine
Start date: 2012-08-01; Completion date: 2019-10-01
Enrollment: 62 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The aim of this study is to compare the efficacy of epidural and IV analgesia in controlling pain in patients undergoing Nuss repair of pectus excavatum. The primary end point will be the mean pain score during postoperative days 0-4.

Detailed description:
Pectus excavatum is a cartilaginous deformity that is the most common congenital anterior chest wall defect in children \[1\]. Children with this disease process often complain of dyspnea, decreased exercise tolerance, and shortness of breath implying a restrictive pulmonary deficit \[2\]. Besides the reported physical limitations, patients can also exhibit manifestations of psychological disturbances (poor body image and depression). Surgical repair has been correlated with enhanced quality of life and improvement in body image\[3\] with recent studies showing improved pulmonary function and cardiac output \[4, 5\]. Surgery initially introduced by Sauerbruch involved rib cartilage resection and sternal osteotomy. This open procedure was further modified and became \[6\] known as the Ravitch procedure. This was the mainstay for repair for over 40 years until the introduction of minimally invasive surgery without rib resection by Nuss and colleagues in 1987 \[7\]. The Nuss repair involves placing an intrathoracic brace through small lateral chest wall incisions aided by thoracoscopy. Similar to bracing the teeth, the Nuss procedure avoids osteotomy or rib cartilage resection \[8\]. The Nuss procedure is the most common minimally invasive procedure in use today to correct this condition and is the current standard of surgical practice. Complications from Nuss repair can range anywhere from 7% to 25% \[9\] and can occur for as long as the bar is in place. Pain control remains a major issue in the perioperative period as patients may require weeks to months of oral narcotics before becoming pain-free after correction of the pectus. A prospective multicenter study reported peak pain scores of 8 on a 0-10 scale in the postoperative period and a mean score of 3 at discharge \[4\]. Postoperative pain after pectus repair has been managed with IV opioids administered by patient controlled analgesia (PCA) devices and by thoracic epidural infusions of combinations of local anesthetics and opioids. It is unclear from published data which method is superior and different tertiary care centers in the USA have a preference for different methods.

Arms: arm 1: One group will have a patient controlled device connected to an intravenous patient controlled analgesia (IV PCA). This device runs a basal infusion of pain medicine (morphine) intravenously with additional allowable patient controlled doses every 10 minutes. arm 2: The other group will have an epidural catheter inserted under sterile conditions in the thoracic epidural space after anesthesia has been induced. This will be connected to a patient controlled epidural analgesia (PCEA) device for postoperative pain control that works in a similar manner except the medication (a combination of local anesthetics and hydromorphone) will be administered in the thoracic epidural space.
Interventions: intervention 1: Hydromorphone intervention 2: Morphine
Intervention descriptions: intervention 1: In keeping with standard practice at the TCH, the position of the thoracic epidural catheter tip will be confirmed by real time fluoroscopy and a single injection of 1 ml of omnipaque 180 mg/mL contrast. In keeping with current practice, a bolus of 0.2% ropivacaine 0.3 ml per kg (maximum dose 20 ml) will be administered in the epidural space to the patients in the TEA group at least 10 minutes prior to surgical incision. intervention 2: This device runs a basal infusion of pain medicine (morphine) intravenously with additional allowable patient controlled doses every 10 minutes

Protocol documents:
Prot_SAP_000.pdf: 
Identifiers: NCT02056301
Unique Protocol ID: H31096
Title: A Comparison Trial Between PCA and Epidural Analgesia for Pectus Excavatum
Repair
Date: 24 April 2019


Institutional Review Board for Baylor College of Medicine and
Affiliated Hospitals
Protocol Number:
H-31096
Status:
Approved
Initial Submit Date: 5/29/2012
Approval Period:
4/24/2019 - 4/23/2020
Section Aa: Title & PI
A1. Main Title
A COMPARISON TRIAL BETWEEN PATIENT CONTROLLED INTRAVENOUS ANALGESIA AND
EPIDURAL ANALGESIA FOR PECTUS EXCAVATUM REPAIR
A2. Principal Investigator
Name:
CHRIS GLOVER
Phone:
832-824-5800
Id:
691844
Fax:
Department:
TCH ANESTHESIOLOGY
Email:
cdglover@bcm.tmc.edu
Center:
Mail Stn:
BCM320
A3. Administrative Contact
Name:
MELISSA CHALLMAN
Phone:
832-826-5600
Id:
181593
Fax:
Email:
karlsten@bcm.tmc.edu
Mail Stn:
BCM320
A3a. Financial Conflict of Interest
Does any member of study personnel (Investigator (including investigator’s spouse and/or dependent children))
that are involved in the design, conduct, or reporting of the research have a Significant Financial Interest (SFI)
that would reasonably appear to be affected by the research for which funding is sought and/or associated with
an entity/business that would reasonably appear to be affected by the research?
No
Section Ab: General Information
A4. Co-Investigators
Name:
NIHAR PATEL
Phone:
832-824-5800
Id:
039846
Fax:
Department:
TCH ANESTHESIOLOGY
Email:
nvp1@bcm.tmc.edu
Center:
Mail Stn:
BCM320
Name:
KIM-PHUONG NGUYEN
Phone:
832-824-5809
Id:
134207
Fax:
832-825-5801
Department:
TCH ANESTHESIOLOGY
Email:
ktn@bcm.tmc.edu
Center:
Mail Stn:
BCM120
Name:
MARK MAZZIOTTI
Phone:
832-822-3135
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Id:
149607
Fax:
832-825-3141
Department:
SURGERY: PEDIATRIC SURGERY DIV.
Email:
mazziott@bcm.tmc.edu
Center:
Mail Stn:
BCM390
Name:
MICHAEL ZELISKO
Phone:
832-824-5800
Id:
160997
Fax:
Department:
TCH ANESTHESIOLOGY
Email:
zelisko@bcm.tmc.edu
Center:
Mail Stn:
BCM320
Name:
MARCIE MEADOR
Phone:
832-826-1924
Id:
161459
Fax:
Department:
TCH ANESTHESIOLOGY
Email:
marcieg@bcm.edu
Center:
Mail Stn:
BCM320
Name:
EDDIE MEDELLIN JR
Phone:
832-824-5866
Id:
174073
Fax:
Department:
TCH ANESTHESIOLOGY
Email:
emedelli@bcm.tmc.edu
Center:
Mail Stn:
BCM320
Name:
TENIOLA SHITTU
Phone:
832-824-5800
Id:
189381
Fax:
Department:
TCH ANESTHESIOLOGY
Email:
shittu@bcm.tmc.edu
Center:
Mail Stn:
BCM320
Name:
MARGARET OWENS-STUBERFIELD
Phone:
832-824-5913
Id:
193093
Fax:
Department:
TCH ANESTHESIOLOGY
Email:
owensstu@bcm.tmc.edu
Center:
Mail Stn:
BCM320
Name:
ANDREW LEE
Phone:
832-822-0761
Id:
194763
Fax:
Department:
TCH ANESTHESIOLOGY
Email:
adlee@bcm.tmc.edu
Center:
Mail Stn:
BCM320
Name:
THIEN-DUY TRAN
Phone:
832-822-3000
Id:
204837
Fax:
Department:
TCH ANESTHESIOLOGY
Email:
thiendut@bcm.tmc.edu
Center:
Mail Stn:
BCM320
Name:
JED NUCHTERN
Phone:
832-822-3135
Id:
671145
Fax:
832-825-3141
Department:
SURGERY: PEDIATRIC SURGERY DIV.
Email:
nuchtern@bcm.tmc.edu
Center:
Mail Stn:
BCM390
Name:
DARRELL L. CASS
Phone:
832-822-3135
Id:
672478
Fax:
832-825-3141
Department:
SURGERY: PEDIATRIC SURGERY DIV.
Email:
dcass@bcm.tmc.edu
Center:
Mail Stn:
BCM390
Name:
HILLARY CLOYD
Phone:
832-824-5800
Id:
Non-Baylor
Fax:
832-825-5801
Institution:
Texas Children's hospital
Email:
hocloyd@texaschildrenshospital.org
Address:
6621 Fannin St. Ste A3300
A5. Funding Source:
Baylor College of Medicine (Internal Funding Only)
A6a. Institution(s) where work will be performed:
TCH: Texas Children's Hospital
A6b. Research conducted outside of the United States:
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Country:
Facility/Institution:
Contact/Investigator:
Phone Number:
If documentation of assurances has not been sent to the Office of Research, please explain:
A7. Research Category:
A8. Therapeutic Intent
Does this trial have therapeutic intent?
Yes
A9. ClinicalTrails.gov Registration
Section B: Exempt Request
B. Exempt From IRB Review
Not Applicable
Section C: Background Information
Pectus excavatum is a cartilaginous deformity that is the most common congenital anterior chest wall defect
in children [1]. Children with this disease process often complain of dyspnea, decreased exercise tolerance,
and shortness of breath implying a restrictive pulmonary deficit [2]. Besides the reported physical limitations,
patients can also exhibit manifestations of psychological disturbances (poor body image and depression).
Surgical repair has been correlated with enhanced quality of life and improvement in body image[3] with
recent studies showing improved pulmonary function and cardiac output [4, 5]. Surgery initially introduced by
Sauerbruch involved rib cartilage resection and sternal osteotomy. This open procedure was further modified
and became [6] known as the Ravitch procedure. This was the mainstay for repair for over 40 years until the
introduction of minimally invasive surgery without rib resection by Nuss and colleagues in 1987 [7]. The Nuss
repair involves placing an intrathoracic brace through small lateral chest wall incisions aided by thoracoscopy.
Similar to bracing the teeth, the Nuss procedure avoids osteotomy or rib cartilage resection [8]. The Nuss
procedure is the most common minimally invasive procedure in use today to correct this condition and is the
current standard of surgical practice. Complications from Nuss repair can range anywhere from 7% to 25% [9]
and can occur for as long as the bar is in place. Pain control remains a major issue in the perioperative period
as patients may require weeks to months of oral narcotics before becoming pain-free after correction of the
pectus. A prospective multicenter study reported peak pain scores of 8 on a 0-10 scale in the postoperative
period and a mean score of 3 at discharge [4]. Postoperative pain after pectus repair has been managed with
IV opioids administered by patient controlled analgesia (PCA) devices and by thoracic epidural infusions of
combinations of local anesthetics and opioids. It is unclear from published data which method is superior and
different tertiary care centers in the USA have a preference for different methods.
Most of the published studies describing the experience at different centers were retrospective, had small
number of patients and did not standardize postoperative care. Soliman noted pain scores were initially higher
in the Post Anesthetic Care Unit in the epidural group, but subsequent scores were lower. In one center there
was a 35% failure rate of epidural analgesia in the first 24 hours, leading this surgical group to question the
value of attempting epidural analgesia. Different results have also been noted in prospective studies. Butkovic
reported that intravenous patient controlled analgesia (PCA) with fentanyl was as effective as epidural
infusions in controlling pain after pectus repair. These authors recommended avoidance of epidural infusions
because of a high failure rate in their hands and because of the potential for neurological complications [10].
In contrast, Weber et al noted pain scores on a visual analog scale were lower in the epidural group
compared to those randomized to morphine PCA and recommended epidural analgesia [11]. In a more recent
randomized controlled trial, there was a longer operating room time, increase in calls to anesthesia, and
greater hospital charges with epidural analgesia after repair of pectus excavatum. Pain scores were lower in
the epidural group early in the postoperative course and patient-controlled analgesia during the later part of
hospital stay. [12] However, their results were confounded by a high failure rate (22%) in the placement and
maintenance of thoracic epidural catheters. In addition, the age distribution of subjects differed with younger
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patients in the IV PCA group. It is well established that younger subjects have less pain than older children
after this operation. There remains a need for a randomized controlled trial to determine which method of
analgesia is better in this patient population.
1. Kelly, R.E., Jr., et al., Pectus excavatum in a 112-year autopsy series: anatomic findings and the effect on
survival. J Pediatr Surg, 2005. 40(8): p. 1275-8. 2. Nuss, D. and R.E. Kelly, Jr., Indications and technique of
nuss procedure for pectus excavatum. Thorac Surg Clin, 2010. 20(4): p. 583-97. 3. Krasopoulos, G., et al.,
Nuss procedure improves the quality of life in young male adults with pectus excavatum deformity. Eur J
Cardiothorac Surg, 2006. 29(1): p. 1-5. 4. Kelly, R.E., Jr., et al., Prospective multicenter study of surgical
correction of pectus excavatum: design, perioperative complications, pain, and baseline pulmonary function
facilitated by internet-based data collection. J Am Coll Surg, 2007. 205(2): p. 205-16. 5. Malek, M.H., et al.,
Cardiovascular function following surgical repair of pectus excavatum: a metaanalysis. Chest 2006. 130(2): p.
506-16. 6. Ravitch, M.M., The operative treatment of pectus excavatum. J Pediatr, 1956. 48(4): p. 465-72. 7.
Nuss, D., et al., A 10-year review of a minimally invasive technique for the correction of pectus excavatum. J
Pediatr Surg, 1998. 33(4): p. 545-52. 8. Nuss, D. and R.E. Kelly, Jr., Minimally invasive surgical correction of
chest wall deformities in children (Nuss procedure). Adv Pediatr, 2008. 55: p. 395-410. 9. Densmore, J.C., et
al., Initial surgical and pain management outcomes after Nuss procedure. J Pediatr Surg, 2010. 45(9): p.
1767-71. 10. Butkovic, D., et al., Postoperative analgesia with intravenous fentanyl PCA vs epidural block
after thoracoscopic pectus excavatum repair in children. Br J Anaesth 2007. 98(5): p. 677-81. 11. Weber, T.,
et al., Superior postoperative pain relief with thoracic epidural analgesia versus intravenous patient-controlled
analgesia after minimally invasive pectus excavatum repair. J Thorac Cardiovasc Surg, 2007. 134(4): p. 865-
70. 12. St. Peter, S.D., et al., Epidural vs patient-controlled analgesia for postoperative pain after pectus
excavatum repair: a prospective, randomized trial. Journal of Pediatric Surgery, 2012. 47(1): p. 148-153.
Section D: Purpose and Objectives
The aim of this study is to compare the efficacy of epidural and IV analgesia in controlling pain in patients
undergoing Nuss repair of pectus excavatum. The primary end point will be the difference in pain scores at
rest and with activity (coughing, deep breathing and movement) during postoperative days 1 -5.
Section E: Protocol Risks/Subjects
E1. Risk Category
Category 2: Research involving greater than minimal risk, but presenting the prospect of direct benefit to the
individual subjects.
E2. Subjects
Gender:
Both
Age:
Adolescent (13-17 yrs), Child (3-12 yrs)
Ethnicity:
Primary Language:
English, Spanish
Groups to be recruited will include:
Patients
Which if any of the following vulnerable populations will be recruited as subjects?
Children
Vulnerable populations require special protections. How will you obtain informed consent, protect subject
confidentiality, and prevent undue coercion?
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Subjects/parents/guardians will be approached in the waiting area on the day of surgery prior to the start of
the procedure. The study will be verbally explained with emphasis on the voluntary nature of study
participation. A written consent form will be provided with ample time given to consider the study. A translator
will be available for Spanish speakers and a Spanish Short form will be used for these subjects. . Participants
will be assured that every effort will be made to protect privacy and to prevent a breach of confidentiality.
E3. Pregnant woman/fetus
Will pregnant women and/or fetuses (as described in 45 CFR 46 Subpart B) be enrolled in the research?
No
E4. Neonates
Will neonates of uncertain viability or nonviable neonates (as described in 45 CFR 46 Subpart B) be enrolled in
the research?
No
E5. Children
Will children be enrolled in the research?
Yes
Section F: Design/Procedure
F1. Design
Select one category that most adequately describes your research:
y) Drug, Phase IV, Single Center
Discuss the research design including but not limited to such issues as: probability of group assignment,
potential for subject to be randomized to placebo group, use of control subjects, etc.
This patient blinded prospective randomized single blind (patient) study will be performed on patients (ages
8-18 years, both males and females, from all ethnic backgrounds) undergoing minimally invasive pectus
excavatum repair at the Texas Children¿s Hospital, Houston, Texas. After obtaining IRB (Institutional Review
Board) approval and written informed consent from each patient or his or her legal representative, 64 patients
scheduled for thoracoscopic repair of pectus excavatum will be randomly assigned into two treatment groups
based on a computer generated random number using Random Allocation Software For Parallel Group
Randomized Trials. There are 2 treatment arms in this study. There are no control or placebo groups and
there is an equal chance of being assigned to either group. One group will have a patient controlled device
connected to an intravenous patient controlled analgesia (IV PCA). This device runs a basal infusion of pain
medicine (morphine) intravenously with additional allowable patient controlled doses every 10 minutes. The
other group will have an epidural catheter inserted under sterile conditions in the thoracic epidural space after
anesthesia has been induced. This will be connected to a patient controlled epidural analgesia (PCEA) device
for postoperative pain control that works in a similar manner except the medication (a combination of local
anesthetics and hydromorphone) will be administered in the thoracic epidural space. The patients will be
blinded to the treatment arm. The epidural catheter will be placed after induction of anesthesia in the thoracic
epidural group by the Pain Service Attending Anesthesiologist, who is a different person from the
anesthesiologist in the room. The Pain Service Attending Anesthesiologist has the most experience in pacing
these catheters. In the IV PCA group, a catheter will be taped to the outside of the skin in the same fashion as
the thoracic epidural catheter but without any needles being used. The anesthesiologist caring for the patient
during surgery will not be blinded. They will care for the patient based on their clinical judgment. However, it
will not be possible to blind the nurses taking care of the patient after surgery as different medications,
infusion rates and programs for limiting drug use are used in the PCA and PCEA devices.
Inclusion Criteria:
1) Patients age 8- 18 years 2) Patients undergoing minimally invasive pectus excavatum repair via Nuss
procedure 3) American Society of Anesthesiology Status I-III
Exclusion Criteria:
1) Refusal of epidural catheter 2) Pregnancy 3) Bleeding History 4) Inability to understand how to use the
PCA device 5) Medication interfering with blood coagulation 6) Patients allergic to local anesthetics 7) Patient
refusal to participate in study 8) Developmental delay
F2. Procedure
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The perioperative management of patients will be in keeping with the current standard practices at the Texas
Children¿s Hospital. All subjects will be asked to assess their baseline pain on a 0-10 verbal rating scale. All
subjects will be told that they will be provided with a device in the postoperative period that will allow them to
receive additional pain medications when they press a button. They will be told to press the button whenever
they need pain medications. Patients will be informed that if they do not get enough relief of pain after
pressing the button, they should inform their nurse who will give additional drugs as required. Prior to the
induction of general anesthesia, all patients will be premedicated with diazepam 0.15 mg / kg body weight
(max dose 10 mg) orally. Anesthesia will be induced via mask inhalational anesthesia with oxygen, nitrous,
and sevoflurane or with IV propofol 2 mg/kg in keeping with the preferences of the patient and the Attending
Anesthesiologist. After placement of intravenous access, rocuronium 0.6 mg / kg and fentanyl 2 mcg/ kg will
be administered, the trachea intubated, and anesthesia maintained with desflurane at an end tidal
concentration of 6.6 % or minimum alveolar concentration (MAC)adjusted to keep heart rate and blood
pressure within 20% of baseline values. All patients will receive a loading bolus of 10 ml / kg of isotonic
Lactated Ringer¿s solution. An opaque envelope containing the group assignment will be opened after
induction of anesthesia. Patients assigned to the IV - PCA group will have an epidural catheter taped to the
skin of the patient¿s back without any needles being inserted. Patients assigned to the thoracic epidural
group (PCEA) group will have a thoracic epidural catheter ( Arrow Epidural Catheter Kit) placed with a 18
gauge Tuohy needle inserted in the T5-6 or T6-7 inter-vertebral space using a loss of resistance to normal
saline in the lateral position. In keeping with standard practice at the TCH, the position of the thoracic epidural
catheter tip will be confirmed by real time fluoroscopy and a single injection of 1 ml of omnipaque 180 mg/mL
contrast. In keeping with current practice, a bolus of 0.2% ropivacaine 0.3 ml per kg (maximum dose 20 ml)
will be administered in the epidural space to the patients in the TEA group at least 10 minutes prior to surgical
incision.
The patients in both groups will receive additional boluses of fentanyl and rocuronium as clinically indicated
according to the judgment of the Attending Anesthesiologist. At the end of the surgical procedure, residual
neuromuscular blockade will be antagonized and the trachea extubated in the operating room when the
Attending Anesthesiologist decides it is safe to do so. The patient will then be transferred to the post
anesthesia recovery room (PACU).
Postoperative Analgesia All groups: In keeping with current practice, supplemental oxygen will be available
for oxygen saturations less the 94% during spontaneous ventilation. All patients will be monitored with full
cardiac ¿respiratory monitors. PCEA group: Analgesia will be maintained with an epidural infusion of 0.15%
ropivacaine with hydromorphone 10mcg/ml at a rate of 0.2 ml / kg/ hour. This will be adjusted via our current
practice to ensure adequate coverage of the surgical incision site. The epidural infusions device will be
programmed to give additional patient controlled bolus doses of 1.5 ml with a lockout of 30 minutes. These
are standard settings for children undergoing this procedure at the TCH. In keeping with current practices, the
thoracic epidural catheter will be removed on the 4th POD. IV PCA group: Patients will receive a continuous
infusion of morphine 0.02 mg/kg/hour IV. The infusion device will be programmed to allow additional patient
controlled doses of morphine, 0.02 mg / kg morphine IV with a lockout time of 10 minutes and calculated 4
hour maximum dosing based on patient weight. This is in keeping with our current practice at Texas
Children's Hospital for IV PCA. On the second postoperative day, the continuous infusion of morphine will be
stopped, but PCA bolus doses continued in keeping with current practices to reduce opioid induced
hyperalgesia and potential for respiratory depression. The epidural catheter that is affixed to the skin will have
tubing attached to a device to continue blinding of the patient.
Protocol for breakthrough pain (both groups): If pain control is not adequate as judged by the patient, they will
receive an additional 0.05 mg / kg bolus of IV morphine with reevaluation at 15 minutes. A second dose of
morphine will be given if the pain scores remain above 4. If the patient continues to have pain, the protocol
permits administration of any other drug necessary for pain relief as judged necessary by the Pain Service
Attending. Transition to oral analgesics: Both groups will receive ketorolac 0.5 mg/kg IV q6hours for a total of
20 doses at POD #5. At the end of the 20 doses, this will be changed to Ibuprofen 400 mg orally every 6
hours. On the morning of the 4th postoperative day, patients will receive an oral combination of hydrocodone
7.5 mg/acetaminophen 325 mg tablets every 4 hours for 24 hours in keeping with current standard practices.
In order to minimize total doses of acetaminophen to below 75 mg/kg/day, patients weighing less than 55 kg
will receive 1 tablet. Patients between 55 and 80 kg will receive 1.5 tablets, and patients greater than 80 kg
will receive 2 tablets. Postoperative Pain Assessment: The intensity of the pain will be assessed at intervals of
4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96 hours using a 10 point numerical rating scale during rest and at
ambulation. Pain scores will be measured at rest and after deep breathing or coughing. These scores are
routinely gathered at these time points by nurses. The total number of analgesic doses that were demanded
and administered doses will be recorded as well for both treatment arms along with the total dose of rescue
morphine required during hospitalization.
The level of sedation will be determined using the University of Michigan Sedation Scale. Incidence of side
effects like nausea, vomiting, pruritis, and urinary retention will be documented through hospitalization. On the
afternoon of the 4th day, the epidural catheters and epidural pumps will be removed from the patient. At thsi
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time point patients will have received 1-2 doses of oral analgesics. Patients will have an option of using the
PCA morphine for severe breakthrough pain. The total amount of rescue morphine boluses and via the PCA
pump required during the transition period will be documented. Patient and Parent Satisfaction Survey: All
parents and patients will complete rate their satisfaction with pain control and their overall experience on a
0-10 scale daily for POD 1-5. These surveys will be collected daily by the research staff.
Section G: Sample Size/Data Analysis
G1. Sample Size
How many subjects (or specimens, or charts) will be used in this study?
Local: 84
Worldwide: 84
Please indicate why you chose the sample size proposed:
The primary endpoint of the study is the mean pain score. In a previous IRB approved retrospective study, the
SD of pain scores in patients undergoing this procedure was 2.3. A difference of 2.0 in the raw pain scores is
considered of clinical importance (Farrar: J Pain Symptom Manage 2003;25:406¿411). With a sample size of
58 in the intent to treat population randomized in a 1: 1 ratio, there is a 90% probability that the study will
detect a treatment difference at a two-sided 0.05 significance level, if the true difference between treatments
is 2.0 units. This is based on the assumption that the standard deviation of the response variable is 2.3. We
plan to recruit 84 patients to allow for a drop out rate of 10%.
G2. Data Analysis
Provide a description of your plan for data analysis. State the types of comparisons you plan (e.g. comparison of
means, comparison of proportions, regressions, analysis of variance). Which is the PRIMARY
comparison/analysis? How will the analyses proposed relate to the primary purposes of your study?
Summary data will be calculated for each group and examined for normal distribution using the Shapiro -Wilks
test. The outcome variables between the groups will be compared with Student¿s t-test where appropriate, for
normally distributed continuous data or by nonparametric tests (Mann Whitney test) if the data are not
normally distributed. Categorical data will be compared by Fisher¿s exact test. Analysis of variance for
repeated measures will be performed to compare differences in pain scores between the two treatment
groups with time. Main effects and interaction between factors will be analyzed by one-way within subject¿s
analysis of variance (ANOVA) and by two-way mixed ANOVA in repeated measures model. Sphericity
assumption will be tested by Mauchly¿s test. Greenhouse¿ Geisser correction to the degrees of freedom and
P-value will be applied if no or mild violation of sphericity is present. If the violation is stronger, the more
conservative Huynh¿Feldt correction will be used. Data will be presented as mean ± SD, or numbers
(percentages). P values less than 0.05 will be considered statistically significant.
The primary end point will be the mean pain scores at rest and with activity (deep breathing, coughing and
movement) during postoperative days 1 -5. Secondary end points will include: a. Total usage of morphine in
mg/kg for postoperative days (POD) 1-5. b. Number of demand doses for PCA/PCEA in the recovery period.
c. Number of rescue analgesia doses on POD 1-5. d. Change in pain scores (delta P) during transition to oral
medications between the 2 groups. e. Side effect incidence of nausea and vomiting, pruritus, urinary retention
(requiring urinary catheterization), and respiratory depression f. Sedation as measured via the University of
Michigan Sedation Scale g. Parental satisfaction and patient satisfaction scores h. Length of stay / time to
discharge In addition to these we will caculate the raw difference in pain intensity (PID; 0¿10 numeric rating
scale [NRS]), percentage difference in pain intensity (%PID; 0¿100% of the NRS), sum of the absolute
difference pain intensity (SPID; sum of PID measurements divided by number of scores), percent of the
maximum total pain relief (%Max TOTPAR). These are standard derived values in pain studies.
Section H: Potential Risks/Discomforts
H1. Potential Risks/Discomforts
Describe and assess any potential risks/discomforts; (physical, psychological, social, legal, or other) and assess
the likelihood and seriousness of such risks:
In this study, we are comparing two techniques, which are currently used in our daily practice at TCH, for
postoperative pain management after minimally invasive thoracoscopic repair of a pectus deformity. No
patient will be receiving general anesthesia, local anesthetic infusion via an epidural and/or postoperative
opioids solely for the purposes of the study, but as part of their routine care. There is no placebo or control
group.
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Patients who do not participate in this study will also require general anesthesia. Postoperative nausea and
vomiting can also occur due to IV opioids (IV PCA group) used intraoperatively and postoperatively. Other
side effects commonly seen with opioids can include respiratory depression, urinary retention, and
constipation. The dose of opioids used in the study is not different from our current standard practice at TCH.
It is possible that patients with effective analgesia from regional anesthesia may have better pain control and
require less opioid in the postoperative period and may have less side effects from opioids. These patients (in
the epidural group) may have more pain when the epidural infusion is stopped.
The risks of epidural placement include local anesthetic toxicity, intravascular injection of local anesthetic
agent, and permanent neurologic injury. Other rare complications can include a high spinal (wet tap),
infection, and bleeding into the epidural space from traumatic placement. It is quite rare for serious cardiac
and neurologic complications to occur with regional anesthesia; and as such these complications are usually
seen in the literature as case reports. 2 prospective French studies put this risk at 1.5 occurences per 10000
cases. Strict asepsis with full barrier precautions is used for placement of an epidural. Placement of the
epidural occurs under general anesthesia to decrease trauma related to placement. This is considered the
standard of care with pediatric patients. Bupivacaine has been routinely used for more than 25 years in
pediatric patients. The upper limits of the dose to be used in this patient population is well established and
available in standard textbooks of pediatrics (Behrman). The amount of local anesthetic used in our study
group is less than 0.3 mg/kg, which is about 10% of the widely accepted maximum dose of the local
anesthetic (bupivacaine 3 mg/kg) (Cote and Behrman). Serious side effects of local anesthetic toxicity from
intravascular injectlon or absorption of local anesthetic agent include heart rate and rhythm changes, low
blood pressure, seizure activity, brain damage and even death. Standard treatment for local anesthetic
toxicity includes 20% intra lipid 1 ml/kg and if required cardiopulmonary resuscitation. The epidural solution is
commonly a mix of local anesthetic and an opioid. Although the dose of the opioid is about 1/10 the
intravenous dose, risks discussed earlier related to opioid exposure can manifest with this small dose in the
epidural space as well.
Additional risks of the study are the small chance of loss of privacy. The data will be coded. No data
identifying the patient will be extracted from the medical records and all data will be kept locked in the offices
of the Principal Investigator. Any electronic version will be kept in a password protected network servers
controlled by the IT services at the TCH. Computers with access to this network are kept in a locked office
where entry is limited to those with an ID key card. This office is located inside the office of the Department of
Anesthesiology at Texas Children's Hospital. Unauthorized individuals would not be able to enter these
facilities. The likelihood of such events is minimal.
H2. Data and safety monitoring plan
Do the study activities impart greater than minimal risk to subjects?
Yes
NOTE: The answer to the questions in H2 requires the completion of the form: 'Section H – Data and Safety
Monitoring Plan' as an attachment in Section S.
H3. Coordination of information among sites for multi-site research
Is the BCM Principal Investigator acting as the SPONSOR-INVESTIGATOR for this multi-site research?
No or Not Applicable
Is BCM the COORDINATING CENTER for this multi-site research?
No or Not Applicable
Section I: Potential Benefits
Describe potential benefit(s) to be gained by the individual subject as a result of participating in the planned
work.
If a patient is assigned to the thoracic epidural (PCEA) group, and if the thoracic epidural analgesia reduces
postoperative pain and the need for postoperative opioids, the child may benefit from less pain and less side
effects from opioids postoperatively. However, it is possible that there will be no benefits from participating in
the study.
Describe potential benefit(s) to society of the planned work.
Data from this study can be used to determine if thoracic epidural or IV PCA provides better pain relief in
patients undergoing the Nuss procedure for pectus repair. Society may benefit from this knowledge as it will
permit other anesthesiologists to use the better technique in the future.
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Do anticipated benefits outweigh potential risks? Discuss the risk-to-benefit ratio.
The risks in this study do not vary from the risks of standard practices at TCH for children undergoing
thoracoscopic Nuss bar placement under general anesthesia with IV PCA or general anesthesia with PCEA.
The additional minor risk of an unlikely loss of privacy is outweighed by the societal benefits from this
knowledge.
Section J: Consent Procedures
J1. Waiver of Consent
Will any portion of this research require a waiver of consent and authorization?
No
J1a. Waiver of requirement for written documentation of Consent
Will this research require a waiver of the requirement for written documentation of informed consent?
No
J2. Consent Procedures
Who will recruit subjects for this study?
PI
PI's staff
Describe how research population will be identified, recruitment procedures, any waiting period between
informing the prospective participant and obtaining consent, steps taken to minimize the possibility of coercion or
undue influence and consent procedures in detail.
Patients presenting for pectus repair will be identified from the Texas Children¿s Hospital operating room
schedule that is routinely available to pediatric anesthesiologists. This will be cross referenced with the
pediatric surgeons operative schedule as these cases are scheduled weeks to months in advance. Potential
subjects will be approached about participation on their visit to our preoperative screening clinic. Voluntary
participation will be emphasized during recruitment of patients. A copy of the IRB approved written consent
form will be given to parents with time allowed to read and consider enrollment. All questions will be fully
answered and another opportunity to raise questions will be presented on the day of surgery in the holding
area.
Are foreign language consent forms required for this protocol?
Yes
Which of the following ways will you document informed consent in languages other than English?
A full-length informed consent document
Short-Form consent documents
J3. Privacy and Intrusiveness
Will the research involve observation or intrusion in situations where the subjects would normally have an
expectation of privacy?
No
J4. Children
Will children be enrolled in the research?
Yes
J5. Neonates
Will non-viable neonates or neonates of uncertain viability be involved in research?
No
J6. Consent Capacity - Adults who lack capacity
Will Adult subjects who lack the capacity to give informed consent be enrolled in the research?
No
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J7. Prisoners
Will Prisoners be enrolled in the research?
No
Section K: Research Related Health Information and Confidentiality
Will research data include identifiable subject information?
Yes
Information from health records such as diagnoses, progress notes, medications, lab or radiology findings, etc.
Yes
Specific information concerning alcohol abuse:
No
Specific information concerning drug abuse:
No
Specific information concerning sickle cell anemia:
No
Specific information concerning HIV:
No
Specific information concerning psychiatry notes:
No
Demographic information (name, D.O.B., age, gender, race, etc.):
Yes
Full Social Security #:
No
Partial Social Security # (Last four digits):
No
Billing or financial records:
No
Photographs, videotapes, and/or audiotapes of you:
No
Other:
No
At what institution will the physical research data be kept?
Texas Children's Hospital
How will such physical research data be secured?
All data will be coded and the key to the code kept in a separate file from the collected data. The key to the
code will be deleted/destroyed after the completion of the study. Physical data files will be kept in the locked
offices of the Principal Investigator, with limited passkey/badge code access restricted. Physical data will also
be maintained in the Anesthesia Dept. in a locked file cabinet with secured badge only access to main entry.
At what institution will the electronic research data be kept?
Electronic data will be stored in a password protected network controlled by the Texas Children's Hospital IT
Dept.
Such electronic research data will be secured via BCM IT Services- provided secured network storage of
electronic research data (Non-Portable devices only):
No
Such electronic research data will be secured via Other:
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Yes, (describe below):
Texas Children's secured server of password only protected access controlled by the Texas Children's IT
Dept.
Will there be anyone besides the PI, the study staff, the IRB and the sponsor, who will have access to identifiable
research data?
No
Please describe the methods of transmission of any research data (including PHI, sensitive, and non-sensitive
data) to sponsors and/or collaborators.
No research data related to and including PHI, sensitive and non-sensitive data will be shared with a sponsor.
When collaborators need to access electronic data, they will log onto the TCH network servers using their
TCH IT issued passwords.
Will you obtain a Certificate of Confidentiality for this study?
No
Please further discuss any potential confidentiality issues related to this study.
Study findings may be published at professional meetings and/or peer reviewed journals. No data identifying
an individual patient will be included in any report of the study.
Section L: Cost/Payment
Delineate clinical procedures from research procedures. Will subject's insurance (or subject) be responsible for
research related costs? If so state for which items subject's insurance (or subject) will be responsible (surgery,
device, drugs, etc). If appropriate, discuss the availability of financial counseling.
Patient will be responsible for costs of anesthesia and analgesia, which can include epidural anesthesia
regardless of study enrollment. There is no additional cost to the patient for participation in the study.
If subjects will be paid (money, gift certificates, coupons, etc.) to participate in this research project, please note
the total dollar amount (or dollar value amount) and distribution plan (one payment, pro-rated payment, paid
upon completion, etc) of the payment.
Dollar Amount:
0
Distribution Plan:
Section M: Genetics
How would you classify your genetic study?
Discuss the potential for psychological, social, and/or physical harm subsequent to participation in this research.
Please discuss, considering the following areas: risks to privacy, confidentiality, insurability, employability,
immigration status, paternity status, educational opportunities, or social stigma.
Will subjects be offered any type of genetic education or counseling, and if so, who will provide the education or
counseling and under what conditions will it be provided? If there is the possibility that a family's pedigree will be
presented or published, please describe how you will protect family member's confidentiality?
Section N: Sample Collection
None
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Section O: Drug Studies
Does the research involve the use of ANY drug* or biologic? (*A drug is defined as any substance that is used to
elicit a pharmacologic or physiologic response whether it is for treatment or diagnostic purposes)
No
Does the research involve the use of ANY gene transfer agent for human gene transfer research?
No
O1. Current Drugs
Is this study placebo-controlled?
Yes
If yes, be sure that you justify the use of the placebo for this research in the space below.
The placebo is actually an infusion device attached to te patient so they are unawre of which treatment arm
they are in. No placebo is actually given or infused into the patient.
Will the research involve a radioactive drug?
No
Section P: Device Studies
Does this research study involve the use of ANY device?
No
Section Q. Consent Form(s)
None
Section R: Advertisements
None
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