Trial Outcomes & Findings for PREMIUM Migraine Trial (NCT NCT00355056)

Last Updated: 2020-07-30

Results Overview

A 50% reduction from the monthly number of migraine attacks during the 60-day baseline phase to the monthly number of migraine attacks during month ten through the twelfth month in the treatment phase (device group versus sham group).

Recruitment status

COMPLETED

Study phase

Target enrollment

230 participants

Primary outcome timeframe

Baseline and months 10-12

Results posted on

2020-07-30

Participant Flow

60 day baseline diary completion prior to randomization.

Participant milestones

Participant milestones
Measure	Sham Procedure Did not receive the closure device, and treated with the current standard of care medical treatment.	Patent Foramen Ovale (PFO) Device Closure Patent foramen ovale (PFO) device Closure procedure using the AMPLATZER PFO Occluder device.
Randomization Period STARTED	107	123
Randomization Period COMPLETED	103	117
Randomization Period NOT COMPLETED	4	6
Optional Patent Foramen Ovale Closure STARTED	0	87
Optional Patent Foramen Ovale Closure COMPLETED	0	84
Optional Patent Foramen Ovale Closure NOT COMPLETED	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Sham Procedure Did not receive the closure device, and treated with the current standard of care medical treatment.	Patent Foramen Ovale (PFO) Device Closure Patent foramen ovale (PFO) device Closure procedure using the AMPLATZER PFO Occluder device.
Randomization Period Early Termination	4	6

Baseline Characteristics

PREMIUM Migraine Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sham Procedure n=107 Participants Participants will not receive the closure device, and will be treated with the current standard of care medical treatment. Will undergo Intracardiac Echo (ICE) in cardiac catheterization lab and simulate PFO closure procedure (sham procedure).	PFO Device Closure n=123 Participants Participants will undergo Intracardiac Echo (ICE) in cardiac catheterization lab and undergo PFO device closure procedure with the AMPLATZER PFO Occluder.	Total n=230 Participants Total of all reporting groups
Age, Continuous	43.72 years STANDARD_DEVIATION 10.16 • n=93 Participants	42.75 years STANDARD_DEVIATION 10.27 • n=4 Participants	43.20 years STANDARD_DEVIATION 10.20 • n=27 Participants
Sex: Female, Male Female	95 Participants n=93 Participants	110 Participants n=4 Participants	205 Participants n=27 Participants
Sex: Female, Male Male	12 Participants n=93 Participants	13 Participants n=4 Participants	25 Participants n=27 Participants
Region of Enrollment United States	107 participants n=93 Participants	123 participants n=4 Participants	230 participants n=27 Participants
International Classification of Headache Disorders (ICH) Migraine with Aura (ICH)	71 participants n=93 Participants	80 participants n=4 Participants	151 participants n=27 Participants
International Classification of Headache Disorders (ICH) Migraine without Aura (ICH)	83 participants n=93 Participants	102 participants n=4 Participants	185 participants n=27 Participants
International Classification of Headache Disorders (ICH) Migraine with and without Aura	47 participants n=93 Participants	58 participants n=4 Participants	105 participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline and months 10-12

Population: Participants included in the analysis were followed for 1-year, had Clinical Event Committee (CEC) adjudicated headache diaries, had greater than or equal to 60% diary compliance during the treatment phase (10-12 months) and were not treatment failures.

Outcome measures

Outcome measures
Measure	Sham Procedure n=103 Participants Did not receive the closure device, and treated with the current standard of care medical treatment.	PFO Device Closure n=117 Participants PFO device Closure procedure using the AMPLATZER PFO Occluder device.
Primary Efficacy Endpoint - Percentage of Subjects With a 50% Reduction From Baseline in the Monthly Number of Migraine Attacks at 12 Months.	32 percentage of subjects	38 percentage of subjects

PRIMARY outcome

Timeframe: Baseline through 12 months

Population: All enrolled subjects who received the device (randomized and Optional PFO Closure group). 5 subjects were considered to have insufficient follow-up and were therefore excluded from the analysis.

Number of subjects who experience a device-related major adverse event (DRMAE) through 12-months of follow-up. This endpoint was analyzed using an as-treated cohort that consists of all enrolled subjects who received the device (randomized and Optional PFO Closure group) and who had follow-up sufficient to adequately assess the DRMAE rate.

Outcome measures

Outcome measures
Measure	Sham Procedure n=205 Participants Did not receive the closure device, and treated with the current standard of care medical treatment.	PFO Device Closure PFO device Closure procedure using the AMPLATZER PFO Occluder device.
Primary Safety Endpoint - Device Related Serious Adverse Event (SAE)	0.49 percentage of participants Interval 0.01 to 2.69	—

SECONDARY outcome

Timeframe: Baseline and months 10-12

Change in the number of migraine days is calculated by the difference in the mean number of migraine days between the baseline assessment period and the treatment phase (months 10-12 post-procedure) for the respective randomization groups.

Outcome measures

Outcome measures
Measure	Sham Procedure n=103 Participants Did not receive the closure device, and treated with the current standard of care medical treatment.	PFO Device Closure n=117 Participants PFO device Closure procedure using the AMPLATZER PFO Occluder device.
Change in Mean Migraine Days/Month	2.0 Migraine days per month Standard Deviation 5.0	3.4 Migraine days per month Standard Deviation 4.4

SECONDARY outcome

Timeframe: Baseline and month 12

Population: 117 device subjects completed the 12 month visit. Only 104 had TCDs that were able to be adjudicated. Of the 13 device subjects with unadjudicated TCDs, 4 did not have valsalva data and 9 did not have TCD data available for various reasons.

Successful Closure by Core Lab Adjudicated Transcranial Doppler (TCD) Grade \<= 2

Outcome measures

Outcome measures
Measure	Sham Procedure n=104 Participants Did not receive the closure device, and treated with the current standard of care medical treatment.	PFO Device Closure PFO device Closure procedure using the AMPLATZER PFO Occluder device.
Percentage of Subjects With Successful PFO Closure at 12-months	82.7 percentage of participants Interval 74.0 to 89.0	—

SECONDARY outcome

Timeframe: 12 months

Population: 101 participants in the sham group and 116 subjects in the PFO device closure group had both baseline and 12-month MIDAS scores available to perform the analysis.

The MIDAS questionnaire measure the impact of headaches on daily living. A total score of 0-5 equals little to no disability, 6-10 equals mild disability, 11-20 equals moderate disability, and a score 21 or greater equals severe disability. The maximum possible score is 276.

Outcome measures

Outcome measures
Measure	Sham Procedure n=101 Participants Did not receive the closure device, and treated with the current standard of care medical treatment.	PFO Device Closure n=116 Participants PFO device Closure procedure using the AMPLATZER PFO Occluder device.
Change in Migraine Disability Assessment (MIDAS) Score From Baseline to 12-months	-17 units on a scale Standard Deviation 36	-22.6 units on a scale Standard Deviation 32.9

SECONDARY outcome

Timeframe: 12 months

Population: Participants were included in the analysis were followed for 1-year, have CEC adjudicated headache diaries, had greater than or equal to 60% diary compliance during the treatment phase (10-12 months) and were not treatment failures.

Outcome measures

Outcome measures
Measure	Sham Procedure n=103 Participants Did not receive the closure device, and treated with the current standard of care medical treatment.	PFO Device Closure n=117 Participants PFO device Closure procedure using the AMPLATZER PFO Occluder device.
Incidence of a 75% Reduction in Migraine Headache Attacks	16.5 percentage of participants	20.5 percentage of participants

SECONDARY outcome

Timeframe: 12 months

Population: Device group subjects who were implanted with the study device and experienced no serious device or procedure-related adverse events.

Procedural success is calculated by the percent of device group subjects who were implanted with the study device and experienced no serious device or procedure-related adverse events.

Outcome measures

Outcome measures
Measure	Sham Procedure n=123 Participants Did not receive the closure device, and treated with the current standard of care medical treatment.	PFO Device Closure PFO device Closure procedure using the AMPLATZER PFO Occluder device.
Procedural Success	94.3 percentage of participants Interval 88.6 to 97.7	—

SECONDARY outcome

Timeframe: 12 months

Population: Percent of PFO closure group subjects who were implanted with the study device, experienced no serious device or procedure-related adverse events and have a core-lab adjudicated TCD Grade at Valsalva ≤ 2 at 1-year. 117 device subjects completed the 12 month visit. Only 104 had TCDs that were able to be adjudicated.

Percent of PFO closure group subjects who were implanted with the study device, experienced no serious device or procedure-related adverse events and have a core-lab adjudicated TCD Grade at Valsalva ≤ 2 at 1-year.

Outcome measures

Outcome measures
Measure	Sham Procedure n=104 Participants Did not receive the closure device, and treated with the current standard of care medical treatment.	PFO Device Closure PFO device Closure procedure using the AMPLATZER PFO Occluder device.
Long-Term Success	80.8 percentage of participants Interval 71.9 to 87.8	—

SECONDARY outcome

Timeframe: 12 months

Population: Participants who experienced an adverse event at or before 12-months post-procedure

Outcome measures

Outcome measures
Measure	Sham Procedure n=107 Participants Did not receive the closure device, and treated with the current standard of care medical treatment.	PFO Device Closure n=123 Participants PFO device Closure procedure using the AMPLATZER PFO Occluder device.
Incidence of All Adverse Events at 12-months	93 participants	105 participants

SECONDARY outcome

Timeframe: 12 months

Population: Participants who experienced a device-related adverse event, as adjudicated by the Data Safety and Monitoring Board (DSMB), at or before 12-months post-procedure.

Outcome measures

Outcome measures
Measure	Sham Procedure n=123 Participants Did not receive the closure device, and treated with the current standard of care medical treatment.	PFO Device Closure PFO device Closure procedure using the AMPLATZER PFO Occluder device.
Incidence of Device-related Adverse Events	31.7 percentage of participants Interval 23.6 to 40.7	—

SECONDARY outcome

Timeframe: 12-months

Outcome measures

Outcome measures
Measure	Sham Procedure n=103 Participants Did not receive the closure device, and treated with the current standard of care medical treatment.	PFO Device Closure n=117 Participants PFO device Closure procedure using the AMPLATZER PFO Occluder device.
Incidence of a 95% Reduction in Migraine Headache Attacks	0.97 percentage of participants	8.55 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: 101 participants in the sham group and 116 subjects in the PFO device closure group had both baseline and 12-month BDI scores available to perform the analysis.

The difference in BDI between baseline and 12-months for the respective randomization groups. The highest possible score of the BDI is 63, which represents extreme depression. The lowest possible score is 0, which represents no depression.

Outcome measures

Outcome measures
Measure	Sham Procedure n=101 Participants Did not receive the closure device, and treated with the current standard of care medical treatment.	PFO Device Closure n=116 Participants PFO device Closure procedure using the AMPLATZER PFO Occluder device.
Change in Beck Depression Inventory (BDI) Scale	-0.3 units on a scale Standard Deviation 7.1	-2.1 units on a scale Standard Deviation 6.5

POST_HOC outcome

Timeframe: 12 months

The term "majority" in "majority of migraine attacks included aura" was defined by the Neurologist (\>50%) at the time of randomization based on a review of the subject's study baseline headache diary and medical history.

Outcome measures

Outcome measures
Measure	Sham Procedure n=39 Participants Did not receive the closure device, and treated with the current standard of care medical treatment.	PFO Device Closure n=40 Participants PFO device Closure procedure using the AMPLATZER PFO Occluder device.
Responder Rate for Subjects in Whom Majority of Attacks Were With Aura	48.7 percentage of subjects	22.5 percentage of subjects

POST_HOC outcome

Timeframe: Baseline through months 10-12

Population: 6 PFO Device Closure Subjects and 3 Sham Procedure Subjects with Aura do not have 12-month follow-up data available.

Complete Cessation of Migraine Attacks, baseline diary compared to months 10-12

Outcome measures

Outcome measures
Measure	Sham Procedure n=74 Participants Did not receive the closure device, and treated with the current standard of care medical treatment.	PFO Device Closure n=68 Participants PFO device Closure procedure using the AMPLATZER PFO Occluder device.
Percentage of Subjects With Migraine With Aura Determined to Have a Complete Cessation of Migraine Attacks According to the International Headache Society (IHS)	10.8 percentage of subjects	1.5 percentage of subjects

Adverse Events

PFO Device Closure

Serious events: 1 serious events

Other events: 119 other events

Deaths: 0 deaths

Sham Procedure

Serious events: 0 serious events

Other events: 103 other events

Deaths: 0 deaths

Optional PFO Closure

Serious events: 0 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PFO Device Closure n=123 participants at risk PFO device Closure procedure using the AMPLATZER PFO Occluder device.	Sham Procedure n=107 participants at risk Did not receive the closure device, and treated with the current standard of care medical treatment.	Optional PFO Closure n=87 participants at risk Subjects randomized to the sham arm and completed their 12-month follow up visit were given the option of PFO closure with the Amplatzer PFO Occluder.
Cardiac disorders Transient atrial fibrillation after device placement	0.81% 1/123 • Number of events 1 • All adverse events were collected from the time of signing informed consent until the 12-month follow-up visit. After the 12-month follow-up visit, serious adverse events and/or device-related events were collected until completion of study requirements.	0.00% 0/107 • All adverse events were collected from the time of signing informed consent until the 12-month follow-up visit. After the 12-month follow-up visit, serious adverse events and/or device-related events were collected until completion of study requirements.	0.00% 0/87 • All adverse events were collected from the time of signing informed consent until the 12-month follow-up visit. After the 12-month follow-up visit, serious adverse events and/or device-related events were collected until completion of study requirements.

Other adverse events

Additional Information

Director, Global Clinical Affairs

St. Jude Medical

Phone: 818-493-3648

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER