Clinical trial NCT03022526
Conditions: Depression, Postpartum Labor Pain
Keywords: Pregnant Analgesia Labor analgesia Epidural Combined spinal epidural
Sponsor: Grace Lim, MD, MS
Start date: 2017-01-01; Completion date: 2019-12-31
Enrollment: 61 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this pilot prospective randomized control trial is to compare the initiation of labor epidural analgesia by combined spinal epidural vs. epidural for the influence on risk for postpartum depression symptoms. Investigators will randomize women to the receipt of CSE or E during labor, after measuring baseline psychological, psychosocial, and psychophysical factors related to pain and depression. The immediate research goals are to understand whether the association between labor pain and PPD is modifiable through the use of tailored anesthetic techniques.

Detailed description:

Arms: arm 1: intrathecal bupivacaine 2.5mg + fentanyl 15mcg followed by infusion (PCEA): bupivacaine 0.083% with fentanyl 2mcg/mL: basal 8mL/hr, demand 8mL, 2 boluses per hour allowed, total maximum hourly allowance 24mL arm 2: epidural bupivacaine 0.083% + fentanyl 2mcg/mL (8mL) followed by fentanyl 100mcg (2mL); follwed by infusion (PCEA): bupivacaine 0.083% with fentanyl 2mcg/mL: basal 8mL/hr, demand 8mL, 2 boluses per hour allowed, total maximum hourly allowance 24mL
Interventions: intervention 1: CSE intervention 2: Epidural intervention 3: Bupivacaine / fentaNYL
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
 
 
 
 
CSE vs. Epidural for Postpartum Depression 
NCT03022526 
July 15, 2020 
 
 
 
 
 
 
 
 
 


NCT03022526 
CSE v. Epidural for Postpartum Depression 
STUDY PROTOCOL: 
The clinical procedure that will be used for research purposes is labor epidural analgesia 
initiation by combined spinal-epidural (CSE) or epidural (E). 
Study participants, prior to enrollment, will have already made a decision for themselves to use 
labor epidural analgesia to manage pain during labor (decision made is one eligibility criteria). 
The study intervention, CSE or E, are both commonly used techniques in the initiation of 
epidural analgesia, but currently the utilization of one or the other of these strategies is left to the 
discretion of the anesthesia clinician and is dictated primarily by clinician preference. Thus an 
RCT will address this level of bias. Both CSE and E can be considered the standard of care for 
any laboring woman requesting labor epidural analgesia. 
BASELINE: At the first encounter, an assessment will include measurements of depression 
(EPDS), anxiety (STAI inventory), resiliency (ER 89), pain catastrophizing (PCS), perceived 
social support (MSPSS) and pain (BPI-long form). For women recruited at the 3rd trimester visit, 
Quantitative sensory testing (QST) will be performed. The pain sensitivity test will involve the 
use of a small pad attached to the participant's arm. The thermal device will gradually heat up 
from the moment the participant feels the heat until the pain sensation becomes uncomfortable; 
the participant is instructed to tell investigators when to discontinue the test at the first moment 
of discomfort, at which time the test is stopped. The pain sensitivity test also includes pressure 
devices to assess pressure pain. These devices are widely and commonly used in clinical pain 
research. From these test, we will determine the participant's sensitivity profile which we will 
use in our study analysis. 
To enhance recruitment, we will also approach women in early labor who have not yet received 
an epidural after consultation with their bedside nurse and once it has been established that they 
meet eligibility criteria. These women will answer the aforementioned baseline surveys but will 
not participate in QST. 
Upon hospital admission for labor and delivery: confirmation of term (>/= 37 weeks) planned 
vaginal delivery will occur. The participant will be randomized to one of two groups: combined 
spinal-epidural (CSE) or epidural (E). Randomization will occur by block allocation. At the 
moment of patient request for labor epidural analgesia, one sealed and opaque envelope 
containing the next assignment group will be opened. The envelopes will be located in a 
designated location in the anesthesia workroom of the birth center, and thus no delays in the 
laboring person's ability to receive the requested epidural is anticipated. Should any delay occur 
for any reason, no randomization will occur and the patient will receive the epidural per routine 
request and clinical flow. Initiation of each labor analgesic strategy will be standardized to 
minimize variability of analgesia, and is outlined on the study figure attached. Management of 
breakthrough pain will be standardized and will occur by the strategy outlined on the study 
figure attached ("supporting documentation"). 
Throughout labor, pain will be assessed hourly using 100mm visual analog scales for both pain 
intensity and pain unpleasantness. Regardless of onset of labor (spontaneous or induction), 
hourly assessments are required to measure with accuracy and density the change in pain that is 


NCT03022526 
CSE v. Epidural for Postpartum Depression 
experienced over time for women in labor, in response to both the progress of labor and any 
changes in response to medications via the epidural infusion. For the entire labor, labor variables 
will be recorded, including sterile vaginal exam (SVE) at the time of epidural request, duration 
of labor (time from admission to unit until time of delivery), number of manual epidural 
supplemental doses, total dose of local anesthetic and epidural opioid required, and the outcome 
of labor -- both maternal (normal spontaneous vaginal delivery, instrumental delivery, cesarean 
delivery, perineal lacerations, total oxytocin dose requirements) and neonatal (sex, Apgar scores, 
need for resuscitation, need for neonatal ICU). Study procedures will continue should the need 
arise for a cesarean delivery or if there are any other complications to the pregnancy/fetus. 
Postpartum measurements will be made as follows: 
Postpartum day 0-2: Within 2 days we will measure co-variates of pain (BPI short), 
breastfeeding (yes/no) and perceived stress (PSS). 
At 6 weeks, we will measure the primary outcome of EPDS score as well as co-variates 
including pain (BPI short), maternal infant attachment (MPAS), parenting self-efficacy (PMP-
SE), child development (ASQ-3), and breastfeeding (yes/no) (i.e. "Are you currently 
breasfteeding? Yes or no.") A margin of 7 days around the 6 week postpartum mark will be 
allowed for the patient to respond. 
At 3 months, we will assess breastfeeding (Y/N), Depression (EPDS), Pain (BPI – Short Form), 
Mother-infant attachment (MPAS), Parenting self-efficacy (PMP-SE), Child development (ASQ-
3). A margin of 7 days around the 3 month postpartum mark will be allowed for the patient to 
respond. 
Should a participant not respond to follow-up surveys at the specified time, we will exclude their 
data from analysis; depending upon the volume and nature of such missing data, we reserve the 
ability to impute missing data if MAR or MNAR. 
Interactions with participants will occur in person, electronically (email), or by phone. 
Investigators will consent participants to retain the ability to re-contact participants at a future 
date for follow-up questions. 
 
 
 
 
 
 
 
 


NCT03022526 
CSE v. Epidural for Postpartum Depression 
STATISTICAL ANALYSIS PLAN: 
The estimated incidence of PPD in U.S. American women is 20%, commensurate with estimates 
of institutional rates of PPD at Magee-Womens Hospital.36 As a pilot, we will target 10% of the 
sample required for a full study. The primary outcome is risk for PPD, measured by EPDS score 
at the 6-week postpartum visit. A sample of 394 participants, 197 in each group, will have 80% 
power to detect a 10% reduction in PPD symptoms at a significance level of 5% (two-tailed). 
With an optimistic estimated attrition of 15%, a full trial would aim to enroll 454 participants, 
227 in each group. For this pilot we will target a sample of 23 patients in each group (total 46), to 
yield 10% of the full study sample. Given a yet unknown attrition rate, we estimate that study 
procedures in a maximum of 60 participants in each group will be the maximum number of 
participants necessary to establish a clear protocol. We will review and refine the protocol every 
5 patients until no further changes to the protocol are made over 5 consecutive participants. We 
will prospectively gather data on screening eligibility, consent and decline rates, crossover rates, 
and provider and subject feedback. 
 
Linear regression will be used to examine the relationship between EPDS scores and treatment 
group, both over time in participants and by group. The relationship between pain and EPDS will 
also be examined using linear regression. T-tests, linear regression, and chi-squared tests will be 
used, where appropriate, to examine the relationships between treatment group and pain, infant 
attachment, infant development, and breastfeeding.