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

• Sponsor: Tufts Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT03678675
• Collaborator: (none)
• Enrollment: 148
• Location: 1
• Arms: 2
• Actual Duration (Months): 37
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Post-operative Pain; Post-partum Pain; Cesarean Section Complications	Drug: Ketorolac	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 148 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized controlled trialRandomized controlled trial
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: The subjects, care providers, and investigators will be blinded to the assignments of groups.
• Primary Purpose: Treatment
• Official Title: Increased Ketorolac Administration After Cesarean Section and Its Effect on Opioid Use: a Randomized Control Trial
• Actual Study Start Date: May 30, 2019
• Actual Primary Completion Date: Jan 31, 2022
• Actual Study Completion Date: Jun 30, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. The Total Morphine Milligram Equivalents (MME) Used in the First 72 Postoperative Hours [Within 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.

Secondary Outcome Measures

1. Number of Participants With a Pain Score Greater Than 3 [2 weeks]

   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. The Number of Patients That Used no Opioid Postoperatively [Within 72 post-operative hours]

   The number of patients in each arm that required no opioids for pain control postoperatively.

3. Postoperative Change in Hematocrit [Change in pre-operative hematocrit to POD1 hematocrit]

   The change in patient hematocrit from baseline to POD1

4. Change in Creatinine [Change in creatinine from POD1 to POD2]

   The change in patient's creatinine from POD1 to POD2

5. Postoperative Satisfaction With Inpatient Pain Control [Inpatient pain control satisfaction as reported at two weeks postpartum]

   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.

6. Postoperative Satisfaction With Their Inpatient Postpartum Care. [Satisfaction with inpatient care as reported at two weeks postpartum]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tufts Medical Center	Boston	Massachusetts	United States	02111

Sponsors and Collaborators

• Tufts Medical Center

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 15, 2022
• Informed Consent Form - Sep 14, 2021

More Information

Publications

None provided.

• Responsible Party: Tufts Medical Center
• ClinicalTrials.gov Identifier: NCT03678675
• Other Study ID Numbers: Ketorolac Pain Study
• First Posted: Sep 19, 2018
• Last Update Posted: Aug 18, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Tufts Medical Center: ketorolac; opiate; cesarean section
• Additional relevant MeSH terms: Pain, Postoperative; Ketorolac

Study Results

Participant Flow

Arm/Group Title	Standard Protocol	Ketorolac Protocol
Arm/Group Description	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.	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. Ketorolac: The intervention is a protocol of scheduled IV Ketorolac administered postoperatively.
Period Title: Overall Study
STARTED	74	74
COMPLETED	74	74
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Standard Protocol	Ketorolac Protocol	Total
Arm/Group Description	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.	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. Ketorolac: The intervention is a protocol of scheduled IV Ketorolac administered postoperatively.	Total of all reporting groups
Overall Participants	74	74	148
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.4 (5)	32.6 (5.2)	32.5 (5)
Sex: Female, Male (Count of Participants)
Female	74 100%	74 100%	148 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	4 5.4%	6 8.1%	10 6.8%
Black	15 20.3%	8 10.8%	23 15.5%
Hispanic	15 20.3%	14 18.9%	29 19.6%
White	32 43.2%	37 50%	69 46.6%
Not reported	8 10.8%	9 12.2%	17 11.5%
Region of Enrollment (participants) [Number]
United States	74 100%	74 100%	148 100%

Outcome Measures

1. Primary Outcome

Title	The Total Morphine Milligram Equivalents (MME) Used in the First 72 Postoperative Hours
Description	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.
Time Frame	Within 72 postoperative hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Protocol	Ketorolac Protocol
Arm/Group Description	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.	Subjects randomized to the Ketorolac protocol will receive the study postoperative pain protocol. This includes 5 doses of IV Ketorolac, scheduled every 6 hours. The first dose is administered in the operating room. Ketorolac: The intervention is a protocol of scheduled IV Ketorolac administered postoperatively.
Measure Participants	74	74
Median (Inter-Quartile Range) [MME]	60.0	30

2. Secondary Outcome

Title	Number of Participants With a Pain Score Greater Than 3
Description	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.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Protocol	Ketorolac Protocol
Arm/Group Description	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.	Subjects randomized to the Ketorolac protocol will receive the study postoperative pain protocol. This includes 5 doses of IV Ketorolac, scheduled every 6 hours. The first dose is administered in the operating room. Ketorolac: The intervention is a protocol of scheduled IV Ketorolac administered postoperatively.
Measure Participants	74	74
Count of Participants [Participants]	40 54.1%	19 25.7%

3. Secondary Outcome

Title	The Number of Patients That Used no Opioid Postoperatively
Description	The number of patients in each arm that required no opioids for pain control postoperatively.
Time Frame	Within 72 post-operative hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Protocol	Ketorolac Protocol
Arm/Group Description	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.	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. Ketorolac: The intervention is a protocol of scheduled IV Ketorolac administered postoperatively.
Measure Participants	74	74
Count of Participants [Participants]	24 32.4%	9 12.2%

4. Secondary Outcome

Title	Postoperative Change in Hematocrit
Description	The change in patient hematocrit from baseline to POD1
Time Frame	Change in pre-operative hematocrit to POD1 hematocrit

Outcome Measure Data

Analysis Population Description

Post-operative day 1 hematocrit was available on 72 patients in the standard group and 73 patients in the ketorolac group.

Arm/Group Title	Standard Protocol	Ketorolac Protocol
Arm/Group Description	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.	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. Ketorolac: The intervention is a protocol of scheduled IV Ketorolac administered postoperatively.
Measure Participants	72	73
Mean (Standard Deviation) [percentage of red blood cells in blood]	-5.5 (3.5)	-5.5 (2.6)

5. Secondary Outcome

Title	Change in Creatinine
Description	The change in patient's creatinine from POD1 to POD2
Time Frame	Change in creatinine from POD1 to POD2

Outcome Measure Data

Analysis Population Description

Post operative day 1 and 2 creatinine was collected on 68 patients in the standard group and 65 patients in the ketorolac group.

Arm/Group Title	Standard Protocol	Ketorolac Protocol
Arm/Group Description	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.	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. Ketorolac: The intervention is a protocol of scheduled IV Ketorolac administered postoperatively.
Measure Participants	68	65
Mean (Standard Deviation) [mg/dL]	.03 (.05)	.59 (.01)

6. Secondary Outcome

Title	Postoperative Satisfaction With Inpatient Pain Control
Description	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.
Time Frame	Inpatient pain control satisfaction as reported at two weeks postpartum

Outcome Measure Data

Analysis Population Description

52 patients in the standard protocol and 52 patients in the ketorolac group responded to the 2 week postpartum survey.

Arm/Group Title	Standard Protocol	Ketorolac Protocol
Arm/Group Description	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.	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. Ketorolac: The intervention is a protocol of scheduled IV Ketorolac administered postoperatively.
Measure Participants	52	52
Count of Participants [Participants]	35 47.3%	29 39.2%

7. Secondary Outcome

Title	Postoperative Satisfaction With Their Inpatient Postpartum Care.
Description	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.
Time Frame	Satisfaction with inpatient care as reported at two weeks postpartum

Outcome Measure Data

Analysis Population Description

52 patients in the standard protocol and 52 patients in the ketorolac group responded to the 2 week postpartum survey.

Arm/Group Title	Standard Protocol	Ketorolac Protocol
Arm/Group Description	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.	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. Ketorolac: The intervention is a protocol of scheduled IV Ketorolac administered postoperatively.
Measure Participants	52	52
Count of Participants [Participants]	39 52.7%	39 52.7%

Adverse Events

Time Frame	Up to 6 weeks postpartum
Arm/Group Title	Standard Protocol		Ketorolac Protocol
Arm/Group Description	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.		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. Ketorolac: The intervention is a protocol of scheduled IV Ketorolac administered postoperatively.
All Cause Mortality
	Standard Protocol		Ketorolac Protocol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/74 (0%)		0/74 (0%)
Serious Adverse Events
	Standard Protocol		Ketorolac Protocol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/74 (1.4%)		1/74 (1.4%)
Nervous system disorders
Headache	0/74 (0%)	0	1/74 (1.4%)	1
Pregnancy, puerperium and perinatal conditions
Endometritis	1/74 (1.4%)	1	0/74 (0%)	0
Other (Not Including Serious) Adverse Events
	Standard Protocol		Ketorolac Protocol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/74 (0%)		0/74 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.