Post-cesarean Analgesia: Comparing Effectiveness of Staggered v. Simultaneous Therapies

Not Applicable

Not yet recruiting

• Conditions: Cesarean Delivery; Postpartum Comfort; Postpartum Pain; Post-operative Pain; NSAIDs; Acetaminophen (D000082)
• Interventions: Drug: Acetaminophen; Drug: NSAID (Ketorolac/Ibuprofen)

• Registration Number: NCT07102641
• Lead Sponsor: Thomas Jefferson University

Brief Summary

Cesarean delivery is a commonly performed surgical procedure associated with worse postpartum pain when compared to vaginal birth. Uncontrolled postpartum pain is associated with increased neonatal and maternal risks. Multimodal non-opioid pain medications, including acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) are the preferred first-line therapies. There is no standard practice, however, on best dosing schedules (ie staggered or different time v. simultaneous or same time). This protocol describes a randomized clinical trial aimed to determine whether staggered dosing of acetaminophen and NSAIDs in superior to simultaneous dosing in controlling post-cesarean pain.

Detailed Description

Cesarean delivery is a commonly performed surgical procedure. The rate of cesarean delivery (CD) is increasing in the US; cesarean accounted for 32% of all births in 2022. Parents who deliver via CD experience more pain than those who have a vaginal birth. Uncontrolled postpartum pain can be associated with an increased risk of physical complications including venous thrombosis, atelectasis, pneumonia as well as increased psychological distress. Poor postpartum pain control can also hinder infant-parental bonding and impact breastfeeding initiation or continuation.

Multiple strategies for post-operative pain management exist including opioid and non-opioid medications. Multimodal non-opioid medications are preferred as first-line therapies due to the short- and long-term risks associated with opioid pain medication. Acetaminophen and ibuprofen are most commonly utilized in the US. A meta-analysis of 21 studies enrolling 1909 post-operative patients examined the efficacy of NSAIDs and parecetamol in combination compared to each drug alone and found a significant reduction in pain intensity for combination therapy compared to each drug alone.

Both acetaminophen and ibuprofen can be given every 6 hours. Practices differ, however, on administering these medications at the same time or in a staggered fashion. To date, there are no trials comparing these different dosing schedules for post-cesarean delivery pain control.

Study Timeline

• Study First Submitted: 2025-07-25
• Study First Submitted QC: 2025-07-31
• Status Verified: 2025-08
• Study Start: 2025-08-01
• Study First Posted: 2025-08-04
• Last Update Submitted: 2025-08-04
• Last Update Posted: 2025-08-07
• Primary Completion: 2027-08
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 825

Inclusion Criteria

• >/= 34 weeks gestation
• Singleton pregnancy
• Delivery via cesarean section under regional anesthesia

Exclusion Criteria

• Contraindication to acetaminophen or NSAIDs
• Current or history of opioid use or misuse
• Intrauterine fetal demise
• Major congenital anomaly
• Conversion to general anesthesia intra-op or planned general anesthesia
• Mid-line vertical skin incision
• Receipt of intraoperative local analgesia such as Transversus Abdominis Plan (TAP) block or wound infiltration

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Staggered	Acetaminophen	Medications administered 3H apart (Staggered)
Staggered	NSAID (Ketorolac/Ibuprofen)	Medications administered 3H apart (Staggered)
Simultaneous	NSAID (Ketorolac/Ibuprofen)	Medications administered at the same time. (Simultaneous)
Simultaneous	Acetaminophen	Medications administered at the same time. (Simultaneous)

Primary Outcome Measures

Name	Time	Method
Postpartum pain control	48 (+/- 2) hours postpartum	Visual analog pain score (VAS) with movement. Scale ranges from 0-10 with 0 indicating no pain and 10 indicating worst possible pain
Opioid consumption	Postpartum Admission (From time of surgery to hospital discharge; typically 2-5 days)	Opioid consumption (in total morphine milligram equivalents (MME))

Secondary Outcome Measures

Name	Time	Method
Postpartum pain at 6 hours	6 hours (+/- 1 hour) post-op	Visual analog pain score with rest. Scale ranges from 0-10 with 0 indicating no pain and 10 indicating worst possible pain
Postpartum pain at 12 hours	12 hours (+/-2 hours) post-op	Visual analog pain score with rest and movement. Scale ranges from 0-10 with 0 indicating no pain and 10 indicating worst possible pain
Postpartum pain at 24 hours	24 hours (+/-2 hours) post-op	Visual analog pain score with rest and movement. Scale ranges from 0-10 with 0 indicating no pain and 10 indicating worst possible pain
Postpartum pain at 48 hours	48 hours (+/- 2 hours) post-op.	Visual analog pain score with rest. Scale ranges from 0-10 with 0 indicating no pain and 10 indicating worst possible pain
Adequate pain control	by 48 hours (+/-2 hours) post-op	Adequate pain control (Visual analog score \<4). Scale ranges from 0-10 with 0 indicating no pain and 10 indicating worst possible pain
Length of stay	Admission to discharge (Typically 2-7 days)	Duration of hospitalization
Infant feeding	At time of hospital discharge (Typically 1- 5 days post-op)	Exclusive breastfeeding, combination feeding, or formula feeding
Patient satisfaction	Post-operative day #2-5.	Patient satisfaction with pain control. Assessed via International Pain Outcomes (IPO) questionnaire. Scores for individual items in this questionnaire range from 0-10, with 0 indicating no symptoms and 10 indicating worst possible symptoms, OR from 0-100% for questions inquiring about time (0% being no time and 100% being all the time).
Opioid Prescription	At hospital discharge (Post-operative day #2-5)	Need for opioid prescription (Yes or No) and amount (MME)
Home opioid	Post-operative day #10-14	Home opioid use in the first week postpartum (Assessed by telephone call)

Trial Locations

Locations (1)

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States