Increased Ketorolac Administration After Cesarean Section and Its Effect on Opioid Use: a Randomized Control Trial

To evaluate the efficacy of increased ketorolac in reducing opioid use after cesarean section.

Study Overview

• Status: Completed
• Conditions: Cesarean Section Complications; Post-operative Pain; Post-partum Pain
• Intervention / Treatment: Drug: Ketorolac

Detailed Description

This was a single-center, randomized, double-blind, parallel-group trial to assess pain management following cesarean section with increased ketorolac versus placebo. All patients undergoing cesarean section with neuraxial anesthesia received two doses of 30mg IV ketorolac postoperatively per hospital protocol and were then randomized to receive an additional four doses of 30 mg of IV ketorolac or placebo every 6 hours. The primary outcome was the total morphine milligram equivalents (MME) used in the first 72 postoperative hours. Secondary outcomes included the number of patients that used no opioid postoperatively, postoperative pain scores, postoperative change in hematocrit and creatinine, and postoperative satisfaction with inpatient care and pain management. A sample size of 74 per group (n=148) was planned.

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women presenting for care at Tufts Medical Center as an outpatient in obstetrics clinic or on Labor and Delivery.
• The subject must have had a cesarean section for any indication at Tufts Medical Center to be randomized to the study
• The subject is willing to have a phone call follow up conversation 2 weeks after their surgery.

Exclusion Criteria:

• Patients with allergy to ketorolac, NSAIDS or aspirin
• Patients with peptic ulcer disease, preexisting kidney or liver disease.
• Duramorph is not used as the anesthetic for the spinal/epidural during the cesarean section.
• Patient is hemodynamically unstable due to hemorrhage.
• Patient requires therapeutic anticoagulation in the post-operative period
• Patients with peripartum cardiomyopathy
• Provider decision to exclude patient.
• Patient diagnosis of chronic hypertension, gestational hypertension, preeclampsia, HELLP syndrome, or eclampsia
• A study subject may participate in another research study while participating in this research study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Standard Protocol; Subjects randomized to the standard group will receive the standard postoperative pain protocol that is currently used at Tufts Medical Center. It includes two doses of IV Ketorolac every 6 hours as needed for postoperative pain. Ibuprofen would be ordered 6 hours following the last dose after the last study drug.
EXPERIMENTAL: Ketorolac Protocol; Subjects randomized to the Ketorolac protocol will receive the study postoperative pain protocol. This includes 6 doses of IV Ketorolac, scheduled every 6 hours. The first dose is administered in the operating room or post-operative care unit.	Drug: Ketorolac; The intervention is a protocol of scheduled IV Ketorolac administered postoperatively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Total Morphine Milligram Equivalents (MME) Used in the First 72 Postoperative Hours	The amount of MME's will be monitored for each group. MME's will be determined by the amount of opiate mediations administered. The MME value can range from 0 to typically 200 MME's, however there is no upper limit of measureable MME's. The MME's for each patient will be a sum of MME's administered throughout the course of the hospitalization.	Within 72 postoperative hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Pain Score Greater Than 3	The patient reported pain scores will be recorded and analyzed for each group. The Pain Score is determined by the patient using a visual analog scale with a range from 0-10, where 0 is no pain at all and 10 is the worst pain imaginable for the patient. Pain scores were collected by postpartum nursing staff per institutional policy. The number of patients with a pain score greater than 3 will be reported. A pain score greater than 3 was chosen as a cutoff as this is the pain score at which an opioid may be indicated for analgesia at our institution.	2 weeks
The Number of Patients That Used no Opioid Postoperatively	The number of patients in each arm that required no opioids for pain control postoperatively.	Within 72 post-operative hours
Postoperative Change in Hematocrit	The change in patient hematocrit from baseline to POD1	Change in pre-operative hematocrit to POD1 hematocrit
Change in Creatinine	The change in patient's creatinine from POD1 to POD2	Change in creatinine from POD1 to POD2
Postoperative Satisfaction With Inpatient Pain Control	Two weeks after cesarean section, subjects were contacted by telephone to complete a survey on postpartum pain management. At least three attempts were made to contact subjects by telephone. In the follow-up phone call, patients were asked to rate their satisfaction with their postpartum care: very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied. The number below describes the number of patients who reported they were "very satisfied" with their care.	Inpatient pain control satisfaction as reported at two weeks postpartum
Postoperative Satisfaction With Their Inpatient Postpartum Care.	Two weeks after cesarean section, subjects were contacted by telephone to complete a survey on their overall postpartum care. At least three attempts were made to contact subjects by telephone. In the follow-up phone call, patients were asked to rate their satisfaction with their postpartum care: very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied. The number below describes the number of patients that reported they were very satisfied with their care.	Satisfaction with inpatient care as reported at two weeks postpartum

Collaborators and Investigators

• Sponsor: Tufts Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 30, 2019
• Primary Completion (ACTUAL): January 31, 2022
• Study Completion (ACTUAL): June 30, 2022

Study Registration Dates

• First Submitted: September 17, 2018
• First Submitted That Met QC Criteria: September 18, 2018
• First Posted (ACTUAL): September 19, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 18, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: cesarean section; ketorolac; opiate
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketorolac
• Other Study ID Numbers: Ketorolac Pain Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No