Trial Outcomes & Findings for pLatelEts And MigRaine iN patEnt foRamen Ovale (NCT NCT03521193)

NCT ID: NCT03521193

Last Updated: 2024-04-19

Results Overview

The evaluation in absolute numbers of patients fully responders, non-responders or with a moderate benefit on migraine symptoms after PFO Closure was performed

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 90 participants
• Primary outcome timeframe: The outcome data were evaluated at 6-months and 12-months after PFO closure and compared to baseline
• Results posted on: 2024-04-19

Participant Flow

Patients were enrolled at Centro Cardiologico Monzino, Milan, Italy between February 2018 and April 2020

After screening of 93 consecutive PFO patients suffering from migraine 15 were excluded due to unwillingness to sign the informed consent, absence of patent PFO at the invasive evaluation, intolerance to antiplatelet therapy. Finally, 78 pts were enrolled in the study and assigned to the PFO Arm; another arm included 12healthy subjects on Aspirin treatment

Participant milestones

Measure	PFO and Migraine Pts 93 consecutive patients addressed to PFO closure and suffering from migraine with aura were prospectively screened. 78 patients were enrolled in the study (T0)	Healthy Subjects on Aspirin 12 healthy subjects on ASA treatment were the control group for phase 2 study
Overall Study STARTED	78	12
Overall Study COMPLETED	62	12
Overall Study NOT COMPLETED	16	0

Reasons for withdrawal

Measure	PFO and Migraine Pts 93 consecutive patients addressed to PFO closure and suffering from migraine with aura were prospectively screened. 78 patients were enrolled in the study (T0)	Healthy Subjects on Aspirin 12 healthy subjects on ASA treatment were the control group for phase 2 study
Overall Study Withdrawal by Subject	8	0
Overall Study non compliant to ASA treatment	8	0

Baseline Characteristics

8 patients refused to continue the study ; 8 patients were not compliant to aspirin treatment, therefore final analysis was performed on 62 patients

Baseline characteristics by cohort

Measure	PFO Patients Enrolled n=78 Participants We enrolled consecutive patients who met the inclusion criteria, symptomatic for migraine alone and Migraine with aura (MHA) patients. The leading indication to PFO closure was a previous TIA or stroke in 37 patients while an off-label indication was offered to 25 patients. These pts underwent PFO closure with the Occlutech Figulla device and treated with dual antiplatelet therapy (Aspirin 100 mg/day + Clopidogrel 75 mg/day), followed by aspirin 100 mg/day alone.	Healthy Subjects n=12 Participants Healthy subjects on aspirin treatment by at least 15 days were the comparative group for platelet aggregation markers and activation markers, platelet procoagulant, circulating serotonin and cell-associated procoagulant potential	Total n=90 Participants Total of all reporting groups
Age, Continuous	40.6 years STANDARD_DEVIATION 12 • n=78 Participants	41 years STANDARD_DEVIATION 10 • n=12 Participants	40.8 years STANDARD_DEVIATION 10 • n=90 Participants
Sex: Female, Male Female	63 Participants n=78 Participants	8 Participants n=12 Participants	71 Participants n=90 Participants
Sex: Female, Male Male	15 Participants n=78 Participants	4 Participants n=12 Participants	19 Participants n=90 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=78 Participants	0 Participants n=12 Participants	0 Participants n=90 Participants
Race (NIH/OMB) Asian	0 Participants n=78 Participants	0 Participants n=12 Participants	0 Participants n=90 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=78 Participants	0 Participants n=12 Participants	0 Participants n=90 Participants
Race (NIH/OMB) Black or African American	0 Participants n=78 Participants	0 Participants n=12 Participants	0 Participants n=90 Participants
Race (NIH/OMB) White	78 Participants n=78 Participants	12 Participants n=12 Participants	90 Participants n=90 Participants
Race (NIH/OMB) More than one race	0 Participants n=78 Participants	0 Participants n=12 Participants	0 Participants n=90 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=78 Participants	0 Participants n=12 Participants	0 Participants n=90 Participants
Region of Enrollment Italy	78 Participants n=78 Participants	12 Participants n=12 Participants	90 Participants n=90 Participants
Migraine	60 Migraine n=78 Participants	0 Migraine n=12 Participants	60 Migraine n=90 Participants
Migraine with aura (MHA)	18 Migraine with aura n=78 Participants	0 Migraine with aura n=12 Participants	18 Migraine with aura n=90 Participants
Patients finally evaluated	62 participants n=62 Participants • 8 patients refused to continue the study ; 8 patients were not compliant to aspirin treatment, therefore final analysis was performed on 62 patients	12 participants n=12 Participants • 8 patients refused to continue the study ; 8 patients were not compliant to aspirin treatment, therefore final analysis was performed on 62 patients	74 participants n=74 Participants • 8 patients refused to continue the study ; 8 patients were not compliant to aspirin treatment, therefore final analysis was performed on 62 patients

PRIMARY outcome

Timeframe: The outcome data were evaluated at 6-months and 12-months after PFO closure and compared to baseline

Population: Analysis performed only in PFO Group patients as not applicable to the control Healthy subjects group

The evaluation in absolute numbers of patients fully responders, non-responders or with a moderate benefit on migraine symptoms after PFO Closure was performed

Outcome measures

Measure	Migraine Assessment After PFO Closure n=62 Participants Migraine symptoms evaluation after PFO closure	Healthy Subjects Evaluation of Platelet thrombin generation potential in HS	PFO Patients at T1 (6 Mos) Evaluation of Platelet thrombin generation potential in PFO patients at T1 (6 mos)
Change in Migraine Characteristics Migraine : Complete Migraine Resolution	43 Participants	—	—
Change in Migraine Characteristics Migraine : Non-responders	2 Participants	—	—
Change in Migraine Characteristics Migraine Symptoms improvement	17 Participants	—	—

PRIMARY outcome

Timeframe: Baseline, 6 months and 12-months after PFO closure

Population: Analysis performed only in PFO Group patients as not applicable to the control Healthy subjects group

The change in migraine severity, incidence and duration with or without aura as measured by the Anzola's score (The score is the expression of the sum of each corresponding value referring to migraine duration, frequency and the presence or absence of aura). The minimum value was 2 and the maximum 9; the higher the value, worse is the migraine classification.

Anzola's score: Duration 0=No pain 1=<6 hours 2=6-12 hours 3=>12 hours Frequency 0=No pain 1=1-4/month 2=5-9/month 3=>10/month Aura 0=No aura

1=Aura in ≥1 attack

Outcome measures

Measure	Migraine Assessment After PFO Closure n=62 Participants Migraine symptoms evaluation after PFO closure	Healthy Subjects Evaluation of Platelet thrombin generation potential in HS	PFO Patients at T1 (6 Mos) Evaluation of Platelet thrombin generation potential in PFO patients at T1 (6 mos)
Migraine Assessment by Anzola's Score Anzola's score @Baseline	7.2 score on a scale Standard Deviation 1.68	—	—
Migraine Assessment by Anzola's Score Anzola's score@6-mos post PFO Closure	1.09 score on a scale Standard Deviation 1.47	—	—
Migraine Assessment by Anzola's Score Anzola's score @12-mos post PFO closure	1.1 score on a scale Standard Deviation 1.57	—	—

SECONDARY outcome

Timeframe: baseline and 6 months after PFO closure

Platelet Thrombin generation potential in migraineurs and healthy subjects

Outcome measures

Measure	Migraine Assessment After PFO Closure n=62 Participants Migraine symptoms evaluation after PFO closure	Healthy Subjects n=15 Participants Evaluation of Platelet thrombin generation potential in HS	PFO Patients at T1 (6 Mos) n=62 Participants Evaluation of Platelet thrombin generation potential in PFO patients at T1 (6 mos)
Platelet Activation (I) Time to peak	32.1 min Standard Deviation 9.5	37.6 min Standard Deviation 10.2	37.8 min Standard Deviation 13
Platelet Activation (I) Lag Time	26.9 min Standard Deviation 8.9	30.6 min Standard Deviation 7.2	32.2 min Standard Deviation 12.4

SECONDARY outcome

Timeframe: Baseline and 6 months after PFO closure

Population: Analysis of platelets' intrinsic characteristics including thrombin-formation capacity, the amount of thrombin and the kinetic rate (peak velocity)

Platelet Thrombin generation Potential in Migraneurs and Healthy subjects

Outcome measures

Measure	Migraine Assessment After PFO Closure n=62 Participants Migraine symptoms evaluation after PFO closure	Healthy Subjects n=12 Participants Evaluation of Platelet thrombin generation potential in HS	PFO Patients at T1 (6 Mos) n=62 Participants Evaluation of Platelet thrombin generation potential in PFO patients at T1 (6 mos)
Platelet Activation (II)	29.1 nMol/L/min Standard Deviation 29	12.3 nMol/L/min Standard Deviation 10.9	17.9 nMol/L/min Standard Deviation 19.9

SECONDARY outcome

Timeframe: baseline and six months after PFO closure

Platelets' endogenous thrombin generation potential in Migraneurs and Healthy subjects

Outcome measures

Measure	Migraine Assessment After PFO Closure n=62 Participants Migraine symptoms evaluation after PFO closure	Healthy Subjects n=12 Participants Evaluation of Platelet thrombin generation potential in HS	PFO Patients at T1 (6 Mos) n=62 Participants Evaluation of Platelet thrombin generation potential in PFO patients at T1 (6 mos)
Platelet Activation (III)	1038 nmol/L x min Standard Deviation 352	781 nmol/L x min Standard Deviation 319	797 nmol/L x min Standard Deviation 373

SECONDARY outcome

Timeframe: Baseline and six-months after PFO closure

Platelets' functional activity measured as the amount of thrombin generation

Outcome measures

Measure	Migraine Assessment After PFO Closure n=62 Participants Migraine symptoms evaluation after PFO closure	Healthy Subjects n=12 Participants Evaluation of Platelet thrombin generation potential in HS	PFO Patients at T1 (6 Mos) n=62 Participants Evaluation of Platelet thrombin generation potential in PFO patients at T1 (6 mos)
Platelet Activation (IV)	115.2 nmol/L Standard Deviation 81.2	63.4 nmol/L Standard Deviation 41.8	77.2 nmol/L Standard Deviation 59.2

SECONDARY outcome

Timeframe: baseline and 6 months after PFO Closure

Population: Patients were analysed at baseline before PFO closure, six months after procedure and compared to healthy subjects

Platelet aggregation was measured on PAP-8 aggregometer (BioData). Briefly, PRP aliquots (250µL) were pipetted into a siliconized glass cuvette, stirred at 1200 rpm at 37°C and stimulated with arachidonic acid (1mM), collagen (2µg/ml), ADP (5µM), TRAP-6 (5µM). Light transmission was recorded for 5 min after stimuli addition and platelet aggregation was reported as maximal percentage of light transmission. Aspirin-treated patients were considered drug responders when platelet aggregation was less than 20% after arachidonic acid (1mM) stimulation.

Outcome measures

Measure	Migraine Assessment After PFO Closure n=62 Participants Migraine symptoms evaluation after PFO closure	Healthy Subjects n=62 Participants Evaluation of Platelet thrombin generation potential in HS	PFO Patients at T1 (6 Mos) n=12 Participants Evaluation of Platelet thrombin generation potential in PFO patients at T1 (6 mos)
Platelet Aggregation (I) ADP (5µM)	153 AUC (AU x min) Interval 92.5 to 210.0	157 AUC (AU x min) Interval 92.0 to 216.0	187 AUC (AU x min) Interval 116.0 to 253.0
Platelet Aggregation (I) TRAP-6 (5µM)	8.5 AUC (AU x min) Interval 5.0 to 14.0	8 AUC (AU x min) Interval 4.0 to 13.0	11 AUC (AU x min) Interval 9.0 to 27.0
Platelet Aggregation (I) Collagen (2µg/ml)	62 AUC (AU x min) Interval 23.7 to 121.2	76.5 AUC (AU x min) Interval 30.2 to 139.5	104 AUC (AU x min) Interval 73.0 to 184.0

SECONDARY outcome

Timeframe: In hospital, six and 12 months follow-up

Population: Clinical evaluation of neurologic recurrences or death was performed during in-hospital stay and subsequent follow-up; Analysis performed only in PFO Group patients as not applicable to the control Healthy subjects group

Absence of TIA and stroke recurrences after PFO closure and during the follow-up

Outcome measures

Measure	Migraine Assessment After PFO Closure n=62 Participants Migraine symptoms evaluation after PFO closure	Healthy Subjects Evaluation of Platelet thrombin generation potential in HS	PFO Patients at T1 (6 Mos) Evaluation of Platelet thrombin generation potential in PFO patients at T1 (6 mos)
Clinical Outcomes In -hospital vascular complications	1 Participants	—	—
Clinical Outcomes device malpositioning/embolization	0 Participants	—	—
Clinical Outcomes Transient atrial fibrillation	5 Participants	—	—
Clinical Outcomes TIA/stroke post PFO Closure	0 Participants	—	—
Clinical Outcomes Recurrent TIAs /stroke @6 months FU	0 Participants	—	—
Clinical Outcomes Recurrent TIAs /stroke @12 months FU	0 Participants	—	—

Adverse Events

Migraine Evaluation in PFO Patients

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Healthy Subjects

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Clinical Trials' Office Chief

Centro Cardiologico Monzino, IRCCS

Phone: +390258002

Email: alessandra.terragni@ccfm.it

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place