Trial Outcomes & Findings for Acute Headache Treatment in Pregnancy: Occipital Nerve Block vs PO Acetaminophen With Caffeine (NCT NCT03951649)

Last Updated: 2023-12-20

Results Overview

Based on guidelines from the International Headache Society the primary outcome is the portion of women who experience resolution of headache or improvement of headache to mild range (VRS ≤ 3) at 2 hours following treatment with Occipital nerve block as compared to acetaminophen/caffeine cocktail.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

62 participants

Primary outcome timeframe

60-300 min

Results posted on

2023-12-20

Participant Flow

Participant milestones

Participant milestones
Measure	Occipital Nerve Block 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Overall Study STARTED	31	31
Overall Study COMPLETED	31	31
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Acute Headache Treatment in Pregnancy: Occipital Nerve Block vs PO Acetaminophen With Caffeine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Occipital Nerve Block n=31 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=31 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)	Total n=62 Participants Total of all reporting groups
Age, Continuous	28.4 years STANDARD_DEVIATION 4.8 • n=5 Participants	27.3 years STANDARD_DEVIATION 5.3 • n=7 Participants	27.9 years STANDARD_DEVIATION 5.1 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	31 Participants n=7 Participants	62 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black, Non-Hispanic	15 Participants n=5 Participants	22 Participants n=7 Participants	37 Participants n=5 Participants
Race/Ethnicity, Customized Race · Hispanic	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Race · White, Non-Hispanic	14 Participants n=5 Participants	6 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment United States	31 participants n=5 Participants	31 participants n=7 Participants	62 participants n=5 Participants
BMI at Randomization	36.4 kg/m^2 STANDARD_DEVIATION 10.5 • n=5 Participants	37.2 kg/m^2 STANDARD_DEVIATION 10.7 • n=7 Participants	36.8 kg/m^2 STANDARD_DEVIATION 10.5 • n=5 Participants
Insurance Status None/Self-pay	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Insurance Status Public	17 Participants n=5 Participants	26 Participants n=7 Participants	43 Participants n=5 Participants
Insurance Status Private	12 Participants n=5 Participants	4 Participants n=7 Participants	16 Participants n=5 Participants
Nulliparous	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Tobacco Use	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Marijuana Use	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Other Illicit Substance Use	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Gestational Age at randomization (weeks)	28.2 weeks STANDARD_DEVIATION 8.3 • n=5 Participants	27.2 weeks STANDARD_DEVIATION 7.5 • n=7 Participants	27.7 weeks STANDARD_DEVIATION 7.9 • n=5 Participants
Chronic Hypertension	9 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants
Diabetes	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Headache prior to pregnancy	12 Participants n=5 Participants	18 Participants n=7 Participants	30 Participants n=5 Participants
Known primary headache disorder Overall	9 Participants n=5 Participants	14 Participants n=7 Participants	23 Participants n=5 Participants
Known primary headache disorder Migraine	8 Participants n=5 Participants	12 Participants n=7 Participants	20 Participants n=5 Participants
Known primary headache disorder Tension	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 60-300 min

Outcome measures

Outcome measures
Measure	Occipital Nerve Block n=31 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=31 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Number of Participants With Response to Occipital Nerve Block in Pregnancy	20 Participants	16 Participants

SECONDARY outcome

Timeframe: 2 hrs

Population: If headache was significantly improved at 1 hour, patient could leave prior to VRS at 2 hours (n=28 total patients). One patient was delivered following ONB instead of discharged due to decision for delivery prior to VRS at 2 hrs.

Visual/verbal Rating Score (VRS). VRS is used to assess pain in patients. With 0 representing no pain at all and 10 representing worst possible pain. Total Minimum score=0 Total Maximum score=10 Higher values represent worse pain. If VRS=0, then the headache pain is considered resolved.

Outcome measures

Outcome measures
Measure	Occipital Nerve Block n=13 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=20 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Response to Treatment Within 2 Hours	6.0 score on a scale Interval 4.0 to 8.0	6.5 score on a scale Interval 2.5 to 8.0

SECONDARY outcome

Timeframe: 4 hours

Outcome measures

Outcome measures
Measure	Occipital Nerve Block n=31 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=31 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Number of Participants With Need for Crossover Treatment	9 Participants	14 Participants

SECONDARY outcome

Timeframe: 60 min

Population: Patients who received crossover treatment. 2 patients in the ONB did not receive crossover as they were with drawn from the study due to decision for delivery. 1 patient in the SC group declined crossover.

Outcome measures

Outcome measures
Measure	Occipital Nerve Block n=9 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=14 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Response to Cross Over Treatment at 60 Min	6 score on a scale Interval 4.0 to 8.0	3 score on a scale Interval 0.0 to 4.0

SECONDARY outcome

Timeframe: 120 min

Outcome measures

Outcome measures
Measure	Occipital Nerve Block n=31 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=31 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Number of Participants With Need for Second Line Treatment	5 Participants	5 Participants

SECONDARY outcome

Timeframe: 180min

Outcome measures

Outcome measures
Measure	Occipital Nerve Block n=5 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=5 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Response to Second Line Treatment at 60 Min	6 score on a scale Interval 4.0 to 7.0	4 score on a scale Interval 3.0 to 5.0

SECONDARY outcome

Timeframe: 5 hours

Population: Patients with a refractory headache. Refractory headache = VRS score of \>3 2 hours after second-line treatment. This prompted Neurology consultation.

Outcome measures

Outcome measures
Measure	Occipital Nerve Block n=4 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=3 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Number of Participants With Need for Neurology Consult	4 Participants	2 Participants

SECONDARY outcome

Timeframe: 7 hours

Outcome measures

Outcome measures
Measure	Occipital Nerve Block n=31 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=31 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Number of Participants With Need for Admission for Treatment of Headache	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 28 days

Population: Patients who responded to specific question at 28 day follow up.

Emergency department for treatment of headache since treatment asked at 28 day follow up

Outcome measures

Outcome measures
Measure	Occipital Nerve Block n=24 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=23 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Number of Participants With Need for Representation for Treatment of Headache With 28 Days	5 Participants	1 Participants

SECONDARY outcome

Timeframe: 28 days

Outcome measures

Outcome measures
Measure	Occipital Nerve Block n=31 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=31 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Number of Participants With Development of Hypertensive Disease of Pregnancy Within 28 Days	9 Participants	4 Participants

SECONDARY outcome

Timeframe: 7 days

Population: Patients who responded to specific question at 7 day follow up.

Outcome measures

Outcome measures
Measure	Occipital Nerve Block n=23 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=23 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Number of Participants With Satisfaction of Response Treatment at 7 Days Strongly satisfied	12 Participants	10 Participants
Number of Participants With Satisfaction of Response Treatment at 7 Days Satisfied	5 Participants	4 Participants
Number of Participants With Satisfaction of Response Treatment at 7 Days Neutral	3 Participants	5 Participants
Number of Participants With Satisfaction of Response Treatment at 7 Days Dissatisfied	1 Participants	1 Participants
Number of Participants With Satisfaction of Response Treatment at 7 Days Very dissatisfied	2 Participants	3 Participants

SECONDARY outcome

Timeframe: 7 days

Population: Patients who responded to specific question at 7 day follow up.

Outcome measures

Outcome measures
Measure	Occipital Nerve Block n=14 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=18 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Duration of Headache Free Period at 7 Days	6 days Interval 0.5 to 7.0	1 days Interval 0.0 to 5.0

SECONDARY outcome

Timeframe: 7 days

Outcome measures

Outcome measures
Measure	Occipital Nerve Block n=31 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=31 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Number of Participants With Development of Hypertensive Disease of Pregnancy Within 7 Days	7 Participants	2 Participants

SECONDARY outcome

Timeframe: 7 days

Population: Number of patients who responded to specific question at 7 day follow up.

Other: Pain at injection site

Outcome measures

Outcome measures
Measure	Occipital Nerve Block n=24 Participants 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=23 Participants Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Number of Participants With Injection Site Complication (Infection, Hematoma, and Ecchymosis)	0 Participants	2 Participants

Adverse Events

Occipital Nerve Block

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Oral Acetaminophen/Caffeine Group

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Occipital Nerve Block n=31 participants at risk 1. Trained OB/GYN providers will perform a physical exam to access location of occipital nerve injection based on palpation of bony landmarks. 2. Site of injection will be cleaned with an alcohol swab. 3. 5cc of 0.5% bupivacaine will be injected into both right and left occipital nerves using a 2.5 inch 25 gauge needle. The needle will be changed between injecting sites. 4. After injection is completed sterile gauze will be held on injection sites for 2-3 min or until bleeding is resolved.	Oral Acetaminophen/Caffeine Group n=31 participants at risk Acetaminophen 650mg PO and Caffeine 100mg PO (both Level A treatments for acute headache)
Pregnancy, puerperium and perinatal conditions Pre-term Birth	0.00% 0/31 • Occurring within 28 days of treatment.	3.2% 1/31 • Number of events 1 • Occurring within 28 days of treatment.
Injury, poisoning and procedural complications Injection Site Complication	0.00% 0/31 • Occurring within 28 days of treatment.	6.5% 2/31 • Number of events 2 • Occurring within 28 days of treatment.

Additional Information

Rachel Sinkey

UAB

Phone: (205) 934-5611

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place