Trial Outcomes & Findings for Opioid Prescription After Cesarean Trial (NCT NCT04296396)

Last Updated: 2023-10-03

Results Overview

Number of participants with moderate to severe pain at 1 week post-discharge; moderate to severe pain is defined as a value of 4 or higher on the "Worst Pain" question of the Brief Pain Inventory (BPI) in the last 24 hours. The BPI measures pain severity on a numeric scale of 0 to 10, with 0 being no pain and 10 being the highest level of pain.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

5521 participants

Primary outcome timeframe

1 week post hospital discharge

Results posted on

2023-10-03

Participant Flow

We conducted this multicenter, randomized, controlled, double blinded trial at 31 hospitals. From September 2020 through March 2022, a total of 18,990 patients underwent screening for randomization. Of the 9,963 eligible patients, 5,521 provided informed consent and were randomized

1 participant in the Fixed Opioid Prescription Arm/Group was reenrolled in the study for a second pregnancy

Participant milestones

Participant milestones
Measure	Individualized Opioid Prescription Protocol (IOPP) Individualized opioid prescription protocol (IOPP) with shared decision making. IOPP will be based on inpatient oral opioid intake during the 24 hour period prior to randomization and should not include the 12 hours immediately after the cesarean.	Fixed Opioid Prescription Fixed amount of opioids (20 tablets of oxycodone 5mg)
Overall Study STARTED	2748	2773
Overall Study COMPLETED	2386	2426
Overall Study NOT COMPLETED	362	347

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Data is missing for one participant in each group.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Individualized Opioid Prescription n=2748 Participants Individualized opioid prescription protocol (IOPP) with shared decision making IOPP will be based on inpatient oral opioid intake during the 24 hour period prior to randomization and should not include the 12 hours immediately after the cesarean.	Fixed Opioid Prescription n=2772 Participants Fixed amount of opioids (20 tablets of oxycodone 5mg)	Total n=5520 Participants Total of all reporting groups
Age, Continuous	30.5 years STANDARD_DEVIATION 5.7 • n=2747 Participants • Data is missing for one participant in each group.	30.3 years STANDARD_DEVIATION 5.8 • n=2771 Participants • Data is missing for one participant in each group.	30.4 years STANDARD_DEVIATION 5.7 • n=5518 Participants • Data is missing for one participant in each group.
Sex: Female, Male Female	2748 Participants n=2748 Participants	2772 Participants n=2772 Participants	5520 Participants n=5520 Participants
Sex: Female, Male Male	0 Participants n=2748 Participants	0 Participants n=2772 Participants	0 Participants n=5520 Participants
Race/Ethnicity, Customized Race/Ethnicity Customized · American Indian/Alaskan Native	24 Participants n=2748 Participants	17 Participants n=2772 Participants	41 Participants n=5520 Participants
Race/Ethnicity, Customized Race/Ethnicity Customized · Asian	118 Participants n=2748 Participants	119 Participants n=2772 Participants	237 Participants n=5520 Participants
Race/Ethnicity, Customized Race/Ethnicity Customized · Non-Hispanic Black	759 Participants n=2748 Participants	746 Participants n=2772 Participants	1505 Participants n=5520 Participants
Race/Ethnicity, Customized Race/Ethnicity Customized · Hispanic	574 Participants n=2748 Participants	589 Participants n=2772 Participants	1163 Participants n=5520 Participants
Race/Ethnicity, Customized Race/Ethnicity Customized · Native Hawaiian/Pacific Islander	9 Participants n=2748 Participants	7 Participants n=2772 Participants	16 Participants n=5520 Participants
Race/Ethnicity, Customized Race/Ethnicity Customized · Non-Hispanic White	1158 Participants n=2748 Participants	1194 Participants n=2772 Participants	2352 Participants n=5520 Participants
Race/Ethnicity, Customized Race/Ethnicity Customized · More than one race	72 Participants n=2748 Participants	78 Participants n=2772 Participants	150 Participants n=5520 Participants
Race/Ethnicity, Customized Race/Ethnicity Customized · Unknown/Not Reported	34 Participants n=2748 Participants	22 Participants n=2772 Participants	56 Participants n=5520 Participants
Number of cesarean deliveries One	1623 Participants n=2747 Participants • Data is missing for one participant from each group.	1630 Participants n=2771 Participants • Data is missing for one participant from each group.	3253 Participants n=5518 Participants • Data is missing for one participant from each group.
Number of cesarean deliveries Two	730 Participants n=2747 Participants • Data is missing for one participant from each group.	735 Participants n=2771 Participants • Data is missing for one participant from each group.	1465 Participants n=5518 Participants • Data is missing for one participant from each group.
Number of cesarean deliveries Three or more	394 Participants n=2747 Participants • Data is missing for one participant from each group.	406 Participants n=2771 Participants • Data is missing for one participant from each group.	800 Participants n=5518 Participants • Data is missing for one participant from each group.
Type of labor No labor	1411 Participants n=2747 Participants • Data is missing for one participant in each group.	1392 Participants n=2771 Participants • Data is missing for one participant in each group.	2803 Participants n=5518 Participants • Data is missing for one participant in each group.
Type of labor Spontaneous	558 Participants n=2747 Participants • Data is missing for one participant in each group.	574 Participants n=2771 Participants • Data is missing for one participant in each group.	1132 Participants n=5518 Participants • Data is missing for one participant in each group.
Type of labor Induced	778 Participants n=2747 Participants • Data is missing for one participant in each group.	805 Participants n=2771 Participants • Data is missing for one participant in each group.	1583 Participants n=5518 Participants • Data is missing for one participant in each group.

PRIMARY outcome

Timeframe: 1 week post hospital discharge

Population: Of 2273 participants in the fixed group, 1 was enrolled in the study for a second pregnancy. Only the first pregnancy was included in the analysis. The primary analysis included participants who completed the highest pain in the last 24 hours on the Brief Pain Inventory at 1 week post-discharge. This data was missing for 230 participants in the individualized opioid prescription group and 219 participants in the fixed group.

Outcome measures

Outcome measures
Measure	Individualized Opioid Prescription n=2518 Participants Individualized opioid prescription protocol and shared decision making 0 to 20 tablets of oxycodone 5mg: Individualized opioid prescription protocol (IOPP) that includes shared decision making. IOPP will be based on inpatient oral opioid intake during the 24 hour period prior to randomization and should not include the 12 hours immediately after the cesarean.	Fixed Opioid Prescription n=2553 Participants fixed opioid prescription of 20 tablets of oxycodone 5mg
Number of Participants With Worst Pain Score of Moderate to Severe on the Brief Pain Inventory	1497 Participants	1535 Participants

SECONDARY outcome

Timeframe: After hospital discharge and up to 90 days postpartum

Population: Of 2273 participants in the fixed group, 1 was enrolled in the study for a second pregnancy. Only the first pregnancy was included in the analysis. This data was missing for 94 participants in the individualized opioid prescription group and 76 participants in the fixed group.

Number of participants who filled one or more opioid prescriptions beyond what was prescribed to them at discharge - measured at ninety days postpartum

Outcome measures

Outcome measures
Measure	Individualized Opioid Prescription n=2654 Participants Individualized opioid prescription protocol and shared decision making 0 to 20 tablets of oxycodone 5mg: Individualized opioid prescription protocol (IOPP) that includes shared decision making. IOPP will be based on inpatient oral opioid intake during the 24 hour period prior to randomization and should not include the 12 hours immediately after the cesarean.	Fixed Opioid Prescription n=2696 Participants fixed opioid prescription of 20 tablets of oxycodone 5mg
Number of Participants Who Filled One or More Opioid Prescriptions Beyond the Amount Prescribed at Discharge	200 Participants	166 Participants

SECONDARY outcome

Timeframe: 90 days postpartum

Population: 94 missing in the IOPP group. 75 missing in the fixed group

Number of opioid prescriptions filled by ninety days postpartum

Outcome measures

Outcome measures
Measure	Individualized Opioid Prescription n=2654 Participants Individualized opioid prescription protocol and shared decision making 0 to 20 tablets of oxycodone 5mg: Individualized opioid prescription protocol (IOPP) that includes shared decision making. IOPP will be based on inpatient oral opioid intake during the 24 hour period prior to randomization and should not include the 12 hours immediately after the cesarean.	Fixed Opioid Prescription n=2697 Participants fixed opioid prescription of 20 tablets of oxycodone 5mg
Number of Opioid Prescriptions Filled Number of participants who filled zero prescriptions	601 Participants	452 Participants
Number of Opioid Prescriptions Filled Number of participants who filled one prescription	1873 Participants	2086 Participants
Number of Opioid Prescriptions Filled Number of participants who filled 2 prescriptions	163 Participants	140 Participants
Number of Opioid Prescriptions Filled Number of participants who filled 3 prescriptions	12 Participants	16 Participants
Number of Opioid Prescriptions Filled Number of participants who filled 4 prescriptions	5 Participants	3 Participants

SECONDARY outcome

Timeframe: 90 days postpartum

Population: Data were missing for 207 participants in the IOPP group and for 180 in the fixed group.

Number of opioid tablets unused from discharge to 90 days postpartum

Outcome measures

Outcome measures
Measure	Individualized Opioid Prescription n=2541 Participants Individualized opioid prescription protocol and shared decision making 0 to 20 tablets of oxycodone 5mg: Individualized opioid prescription protocol (IOPP) that includes shared decision making. IOPP will be based on inpatient oral opioid intake during the 24 hour period prior to randomization and should not include the 12 hours immediately after the cesarean.	Fixed Opioid Prescription n=2592 Participants fixed opioid prescription of 20 tablets of oxycodone 5mg
Number of Opioid Tablets Unused Since Discharge	2 tablets Interval 0.0 to 8.0	7 tablets Interval 0.0 to 16.0

SECONDARY outcome

Timeframe: 2 weeks post discharge

Total morphine milligram equivalents (MME) used from discharge to 2 weeks post-discharge. MME is the amount of milligrams of morphine an opioid dose is equal to when prescribed. Calculating MME accounts for differences in opioid drug type and strength.

Outcome measures

Outcome measures
Measure	Individualized Opioid Prescription n=2748 Participants Individualized opioid prescription protocol and shared decision making 0 to 20 tablets of oxycodone 5mg: Individualized opioid prescription protocol (IOPP) that includes shared decision making. IOPP will be based on inpatient oral opioid intake during the 24 hour period prior to randomization and should not include the 12 hours immediately after the cesarean.	Fixed Opioid Prescription n=2772 Participants fixed opioid prescription of 20 tablets of oxycodone 5mg
Number of Morphine Milligram Equivalents Used at 2 Weeks Post Discharge	22.5 morphine milligram equivalent Interval 0.0 to 75.0	37.5 morphine milligram equivalent Interval 0.0 to 97.5

SECONDARY outcome

Timeframe: 2 weeks post discharge

Population: Data were missing for 234 participants in the IOPP group and for 286 in the fixed group

Pain severity scores assessed on the Brief Pain Inventory numeric scale from 0 to 10 at 2 weeks post-discharge. The BPI measures pain severity on a numeric scale of 0 to 10, with 0 being no pain and 10 being the highest level of pain.

Outcome measures

Outcome measures
Measure	Individualized Opioid Prescription n=2514 Participants Individualized opioid prescription protocol and shared decision making 0 to 20 tablets of oxycodone 5mg: Individualized opioid prescription protocol (IOPP) that includes shared decision making. IOPP will be based on inpatient oral opioid intake during the 24 hour period prior to randomization and should not include the 12 hours immediately after the cesarean.	Fixed Opioid Prescription n=2486 Participants fixed opioid prescription of 20 tablets of oxycodone 5mg
Worst Pain Severity Score at 2 Weeks Post Discharge	2.0 score on a scale Interval 1.0 to 4.0	2.0 score on a scale Interval 1.0 to 4.0

SECONDARY outcome

Timeframe: 2 weeks post discharge

Population: Data were missing for 234 participants in the IOPP group and for 286 in the fixed group

Pain interference scores ≥ 4 on the Brief Pain Inventory (numeric scale from 0 to 10) at 2 weeks post-discharge. The BPI measures pain severity on a numeric scale of 0 to 10, with 0 being no pain and 10 being the highest level of pain. This outcome asks participants to indicate their pain scores for the week prior to completing the inventory.

Outcome measures

Outcome measures
Measure	Individualized Opioid Prescription n=2514 Participants Individualized opioid prescription protocol and shared decision making 0 to 20 tablets of oxycodone 5mg: Individualized opioid prescription protocol (IOPP) that includes shared decision making. IOPP will be based on inpatient oral opioid intake during the 24 hour period prior to randomization and should not include the 12 hours immediately after the cesarean.	Fixed Opioid Prescription n=2486 Participants fixed opioid prescription of 20 tablets of oxycodone 5mg
Pain Interference Score ≥ 4 at 2 Weeks Post Discharge	415 Participants	427 Participants

SECONDARY outcome

Timeframe: 2 weeks post discharge

Number of participants who indicated an improved global impression of change in overall pain at 2 weeks post-discharge. This represents a selection on a multiple choice survey question with the response options: very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse.

Outcome measures

Outcome measures
Measure	Individualized Opioid Prescription n=2528 Participants Individualized opioid prescription protocol and shared decision making 0 to 20 tablets of oxycodone 5mg: Individualized opioid prescription protocol (IOPP) that includes shared decision making. IOPP will be based on inpatient oral opioid intake during the 24 hour period prior to randomization and should not include the 12 hours immediately after the cesarean.	Fixed Opioid Prescription n=2509 Participants fixed opioid prescription of 20 tablets of oxycodone 5mg
Number of Participants Who Indicated an Improved Global Impression of Change	2436 Participants	2436 Participants

SECONDARY outcome

Timeframe: 6 weeks postpartum

Population: 2856 and 2889. Data is missing for 102 neonates in the IOPP group and 92 neonates in the fixed opioid group.

Proportion of infants readmitted to the hospital

Outcome measures

Outcome measures
Measure	Individualized Opioid Prescription n=2754 Participants Individualized opioid prescription protocol and shared decision making 0 to 20 tablets of oxycodone 5mg: Individualized opioid prescription protocol (IOPP) that includes shared decision making. IOPP will be based on inpatient oral opioid intake during the 24 hour period prior to randomization and should not include the 12 hours immediately after the cesarean.	Fixed Opioid Prescription n=2793 Participants fixed opioid prescription of 20 tablets of oxycodone 5mg
Infant Hospital Readmissions	59 Participants	63 Participants

SECONDARY outcome

Timeframe: 6 weeks postpartum

Population: data is missing for 252 participants in the IOPP group and 276 participants in the fixed prescription group

The proportion of participants with a score of 13 or higher on the Edinburgh Postnatal Depression Scale. The minimum score is 0 and the maximum score is 30. Higher scores indicate worse outcomes, where persons scoring about 13 are likely to be suffering from a depressive illness. The scale indicates how the respondent has felt during the previous week.

Outcome measures

Outcome measures
Measure	Individualized Opioid Prescription n=2496 Participants Individualized opioid prescription protocol and shared decision making 0 to 20 tablets of oxycodone 5mg: Individualized opioid prescription protocol (IOPP) that includes shared decision making. IOPP will be based on inpatient oral opioid intake during the 24 hour period prior to randomization and should not include the 12 hours immediately after the cesarean.	Fixed Opioid Prescription n=2496 Participants fixed opioid prescription of 20 tablets of oxycodone 5mg
Maternal Depression Score ≥ 13	185 Participants	191 Participants

Adverse Events

Individualized Opioid Prescription (IOPP) -Mother

Serious events: 133 serious events

Other events: 166 other events

Deaths: 0 deaths

Fixed Opioid Prescription -Mother

Serious events: 96 serious events

Other events: 186 other events

Deaths: 0 deaths

Individualized Opioid Prescription (IOPP) -Neonates/Infants

Serious events: 37 serious events

Other events: 0 other events

Deaths: 11 deaths

Fixed Opioid Prescription - Neonates/Infants

Serious events: 30 serious events

Other events: 0 other events

Deaths: 8 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Individualized Opioid Prescription (IOPP) -Mother n=2748 participants at risk Individualized opioid prescription protocol (IOPP) with shared decision making. IOPP will be based on inpatient oral opioid intake during the 24 hour period prior to randomization and should not include the 12 hours immediately after the cesarean.	Fixed Opioid Prescription -Mother n=2772 participants at risk Fixed amount of opioids (20 tablets of oxycodone 5mg)	Individualized Opioid Prescription (IOPP) -Neonates/Infants n=2856 participants at risk Neonates/infants of participants in the Individualized opioid prescription protocol (IOPP) with shared decision making group.	Fixed Opioid Prescription - Neonates/Infants n=2889 participants at risk Neonates/infants of participants in the fixed opioid prescription group.
General disorders Drowsiness	6.0% 166/2748 • Number of events 166 • Adverse events were collected from the time of randomization at delivery through 90 days postpartum (a period of 90 days). Adverse events were collected for maternal participants and their neonates.	6.7% 186/2772 • Number of events 186 • Adverse events were collected from the time of randomization at delivery through 90 days postpartum (a period of 90 days). Adverse events were collected for maternal participants and their neonates.	0.00% 0/2856 • Adverse events were collected from the time of randomization at delivery through 90 days postpartum (a period of 90 days). Adverse events were collected for maternal participants and their neonates.	0.00% 0/2889 • Adverse events were collected from the time of randomization at delivery through 90 days postpartum (a period of 90 days). Adverse events were collected for maternal participants and their neonates.

Additional Information

MFMU Principal Investigator

George Washington University Biostatistics Center

Phone: 301-881-9260

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Publication restrictions are in place

Restriction type: OTHER