Trial Outcomes & Findings for Occipital Blocks for Acute Migraine (NCT NCT03526874)

Results Overview

By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Numeric Rating Scale (NRS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. NRS scale is a 0 to 10 scale, with 0 meaning no pain and 10 meaning "the worse pain imaginable". A mean change of 2-points has been shown to be clinically relevant.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

63 participants

Primary outcome timeframe

Pre-injection (*Baseline*) and 30 minutes Post-injection

Results posted on

2025-04-17

Participant Flow

Subjects were contacted over the phone and, if interested, verbally consented and prescreened. Potentially eligible subjects were schedule for a visit. After signing consent during the study visit, eligibility was assessed. Approximately 438 patients were prescreened, and we have approached 140. Of those 63 were recruited and 58 randomized (5 screen failed after consent)).

Lidocaine cream lead in. If the subject responded to lidocaine cream application after 30 minutes they were not randomized. All eligible subjects were randomized.

Participant milestones

Participant milestones
Measure	Greater Occipital Nerve (GON) Block With Lidocaine Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Overall Study STARTED	29	29
Overall Study COMPLETED	29	29
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Occipital Blocks for Acute Migraine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.	Total n=58 Participants Total of all reporting groups
Age, Continuous	15.80 years STANDARD_DEVIATION 2.00 • n=5 Participants	16.19 years STANDARD_DEVIATION 1.52 • n=7 Participants	16.00 years STANDARD_DEVIATION 1.80 • n=5 Participants
Sex/Gender, Customized Gender · Female	21 Participants n=5 Participants	23 Participants n=7 Participants	44 Participants n=5 Participants
Sex/Gender, Customized Gender · Male	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Sex/Gender, Customized Gender · Non-binary	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Sex/Gender, Customized Gender · Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	26 Participants n=7 Participants	47 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=5 Participants	26 Participants n=7 Participants	51 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	29 participants n=5 Participants	29 participants n=7 Participants	58 participants n=5 Participants
Migraine Diagnosis Episodic Migraine	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Migraine Diagnosis Chronic migraine	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-injection (*Baseline*) and 30 minutes Post-injection

By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Numeric Rating Scale (NRS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. NRS scale is a 0 to 10 scale, with 0 meaning no pain and 10 meaning "the worse pain imaginable". A mean change of 2-points has been shown to be clinically relevant.

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS)	2.3 score on a scale Standard Error 1.9	1.1 score on a scale Standard Error 1.9

PRIMARY outcome

Timeframe: Pre-injection and 30 minutes Post-injection

By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Visual Analog Scale (VAS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. VAS scale is a 0 to 100 visual scale, with 0 meaning no pain and 100 meaning "the worse pain imaginable".

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS)	24.97 score on a scale Standard Error 4.09	12.86 score on a scale Standard Error 3.61

PRIMARY outcome

Timeframe: Pre-injection (*Baseline*) and 30 minutes Post-injection

Population: Overall number is divided between the different sex subcategories for analysis.

By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Numeric Rating Scale (NRS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. By sex. NRS scale is a 0 to 10 scale, with 0 meaning no pain and 10 meaning "the worse pain imaginable". A mean change of 2-points has been shown to be clinically relevant.

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Sex Female	2.5 score on a scale Standard Deviation 2	1 score on a scale Standard Deviation 1.8
Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Sex Male	2 score on a scale Standard Deviation 1.8	2 score on a scale Standard Deviation 2

PRIMARY outcome

Timeframe: Pre-injection and 30 minutes Post-injection

Population: Overall number is divided between the different sex subcategories for analysis.

By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Visual Analog Scale (VAS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. By sex. VAS scale is a 0 to 100 visual scale, with 0 meaning no pain and 100 meaning "the worse pain imaginable".

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Sex Female	25.5 score on a scale Standard Deviation 23	12 score on a scale Standard Deviation 19.6
Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Sex Male	23.6 score on a scale Standard Deviation 20.6	10.3 score on a scale Standard Deviation 19

PRIMARY outcome

Timeframe: Pre-injection (*Baseline*) and 30 minutes Post-injection

Population: Overall number is divided between the different ethnic subcategories for analysis.

By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Numeric Rating Scale (NRS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. By ethnicity. NRS scale is a 0 to 10 scale, with 0 meaning no pain and 10 meaning "the worse pain imaginable". A mean change of 2-points has been shown to be clinically relevant.

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=28 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Ethnicity Hispanic	1.3 score on a scale Standard Deviation 1.5	-0.5 score on a scale Standard Deviation 0.7
Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Ethnicity Non-Hispanic	2.5 score on a scale Standard Deviation 2	1.2 score on a scale Standard Deviation 1.9

PRIMARY outcome

Timeframe: Pre-injection and 30 minutes Post-injection

Population: Overall number is divided between the different ethnic subcategories for analysis.

By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Visual Analog Scale (VAS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. By ethnicity. VAS scale is a 0 to 100 visual scale, with 0 meaning no pain and 100 meaning "the worse pain imaginable".

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=28 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Ethnicity Non-Hispanic	27.5 score on a scale Standard Deviation 22.2	14.5 score on a scale Standard Deviation 19.8
Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Ethnicity Hispanic	9 score on a scale Standard Deviation 14.4	-3.5 score on a scale Standard Deviation 4.9

PRIMARY outcome

Timeframe: Pre-injection (*Baseline*) and 30 minutes Post-injection

Population: Overall number is divided between the different race subcategories for analysis.

By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Numeric Rating Scale (NRS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. By race. NRS scale is a 0 to 10 scale, with 0 meaning no pain and 10 meaning "the worse pain imaginable". A mean change of 2-points has been shown to be clinically relevant.

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Race Asian	0 score on a scale Standard Deviation 0	0 score on a scale Standard Deviation 0
Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Race Black	4 score on a scale Standard Deviation 2.8	2 score on a scale Standard Deviation 2.6
Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Race White	2.4 score on a scale Standard Deviation 1.9	0.8 score on a scale Standard Deviation 1.6
Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Race Multiple races	1 score on a scale Standard Deviation 1.4	5 score on a scale Standard Deviation 0

PRIMARY outcome

Timeframe: score on a scale

Population: Overall number is divided between the different race subcategories for analysis.

By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Visual Analog Scale (VAS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. By race. VAS scale is a 0 to 100 visual scale, with 0 meaning no pain and 100 meaning "the worse pain imaginable".

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Race Asian	-12 score on a scale Standard Deviation 0	3 score on a scale Standard Deviation 0
Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Race Black	26 score on a scale Standard Deviation 26.9	21.3 score on a scale Standard Deviation 11.7
Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Race White	27.2 score on a scale Standard Deviation 21.6	10 score on a scale Standard Deviation 17.4
Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Race Multiple races	14 score on a scale Standard Deviation 21.2	66 score on a scale Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Missing values were omitted from testing.

The PedMIDAS will assess changes in functional disability due to headache. The PedMIDAS is a validated 6-question scale that captures headache-related disability-across multiple domains of functioning including school, home, social, and recreational-for pediatric and adolescent aged patients over 3 months. The instrument measures the number of days in which subjects missed activities due to headache or migraine. The measure yields a total score by summing items ranging from 0 to 90 day. The higher the score the higher the disability. Change in total score (total at week 4 minus total at baseline) is reported.

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=28 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=25 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Change From Baseline Disability	0.036 change of score on a scale Standard Error 8.46	-13.36 change of score on a scale Standard Error 9.39

SECONDARY outcome

Timeframe: Baseline and Day 7

Population: Missing values were omitted from testing.

The Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (Short Form) will assess changes in functional disability due to headache. The PROMIS Pain Interference (Short Form) measures the self-reported consequences of pain on relevant aspects of the subject's life over the past seven days. A pain item pool was developed to yield scores on a T-score scale with a mean of 50 and standard deviation of 10. A higher PROMIS T-score represents more pain interference, a T-score of 60 is one standard deviation (SD) worse than average. By comparison, a pain interference T-score of 40 is one SD better than average.

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=28 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=24 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Change From Baseline Disability to Day 7	5.78 t-score Standard Error 1.54	2.11 t-score Standard Error 1.09

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Missing values were omitted from testing.

The PROMIS Pain Interference (Short Form) will assess changes in functional disability due to headache. The PROMIS Pain Interference (Short Form) measures the self-reported consequences of pain on relevant aspects of the subject's life over the past seven days. A pain item pool was developed to yield scores on a T-score scale with a mean of 50 and standard deviation of 10. A higher PROMIS T-score represents more pain interference, a T-score of 60 is one SD worse than average. By comparison, a pain interference T-score of 40 is one SD better than average.

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=28 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=25 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Change From Baseline Disability to Week 4	5.05 T-score Standard Error 1.75	2.06 T-score Standard Error 1.35

SECONDARY outcome

Timeframe: 30 minutes Post-injection

The measurement involves resolution of headache pain within 30 minutes after injection and prior to any rescue medications. Data will be collected prospectively from subjects, at the study visit.

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Percentage of Subjects With Pain Freedom	5 Participants	2 Participants

SECONDARY outcome

Timeframe: 30 minutes Post-injection

The measurement involves improvement in headache from "severe or moderate" to "none or mild" within 30 minutes and before any rescue medications. Data will be collected prospectively from subjects at the study visit.

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Percentage of Subjects With Pain Relief or Headache Response	15 Participants	7 Participants

SECONDARY outcome

Timeframe: 24 hours Post-injection

The measurement involves being pain-free within 30 minutes and lasting at least 24 hours, with no use of rescue medication and no relapse or recurrence. Data will be collected prospectively from subjects, via text, in an electronic headache diary.

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Percentage of Subjects With Sustained Pain Freedom	4 Participants	0 Participants

SECONDARY outcome

Timeframe: 24 hours Post-injection

The measurement involves having pain-relief within 30 minutes and lasting at least 24 hours, with no use of rescue medication and no relapse or recurrence. Data will be collected prospectively from subjects, via text, in an electronic headache diary.

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Percentage of Subjects With Sustained Pain Relief	7 Participants	1 Participants

SECONDARY outcome

Timeframe: 24 hours Post-injection

The presence or absence of photophobia, phonophobia, and nausea will be collected from subjects prospectively, via text, in an electronic headache diary.

Outcome measures

Outcome measures
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 Participants Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 Participants Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Percentage of Subjects With Freedom From All Symptoms of Migraine	14 Participants	6 Participants

Adverse Events

Greater Occipital Nerve (GON) Block With Lidocaine

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Greater Occipital Nerve (GON) Block With Saline

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 participants at risk Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 participants at risk Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Immune system disorders Anaphylaxis	0.00% 0/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	3.4% 1/29 • Number of events 1 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.

Other adverse events

Other adverse events
Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 participants at risk Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 participants at risk Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
General disorders Pre-syncope/syncope	6.9% 2/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	10.3% 3/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Nervous system disorders Confusion	0.00% 0/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	3.4% 1/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Nervous system disorders Worse headache pain	72.4% 21/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	89.7% 26/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Nervous system disorders Feeling dizzy	72.4% 21/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	72.4% 21/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Gastrointestinal disorders Feeling sick to your stomach	55.2% 16/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	69.0% 20/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Nervous system disorders Feeling worried or panicky	58.6% 17/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	72.4% 21/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Nervous system disorders Numbness	62.1% 18/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	37.9% 11/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Immune system disorders Rash	3.4% 1/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	3.4% 1/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Injury, poisoning and procedural complications Injection site problems	27.6% 8/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	55.2% 16/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.

Additional Information

Dr. Christina Szperka

Children's Hospital of Philadelphia

Phone: 12155901719

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Greater Occipital Nerve (GON) Block With Lidocaine n=29 participants at risk Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Lidocaine Hydrochloride 2 mg/mL Injectable Solution: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.	Greater Occipital Nerve (GON) Block With Saline n=29 participants at risk Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. Lidocaine 4% Topical Application Cream \[LMX 4\]: Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve. Normal Saline: Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
General disorders Pre-syncope/syncope	6.9% 2/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	10.3% 3/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Nervous system disorders Confusion	0.00% 0/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	3.4% 1/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Nervous system disorders Worse headache pain	72.4% 21/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	89.7% 26/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Nervous system disorders Feeling dizzy	72.4% 21/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	72.4% 21/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Gastrointestinal disorders Feeling sick to your stomach	55.2% 16/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	69.0% 20/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Nervous system disorders Feeling worried or panicky	58.6% 17/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	72.4% 21/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Nervous system disorders Numbness	62.1% 18/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	37.9% 11/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Immune system disorders Rash	3.4% 1/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	3.4% 1/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.
Injury, poisoning and procedural complications Injection site problems	27.6% 8/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.	55.2% 16/29 • Adverse events (AEs) were collected from the time of the lead in treatment (lidocaine cream) application until 28days post-visit, up to 29 days. AEs were collected by RedCap survey, contact with the family and Epic chart review up until 28 days post visit. Serious adverse events (SAEs) were reported to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) within 24h of knowledge of the event. AEs were reported to the IRB at the next continuing review.