BEVACIZUMAB for Cerebral arteriovenous malformation

Inclusion criteria

• {"criterion_text":"- Patient over 18 years"}
• {"criterion_text":"- Affiliated or beneficiary of a social security plan"}
• {"criterion_text":"- With a symptomatic cerebral AVM (chronic headache, focal neurological deficit, cognitive impairment, epilepsy) of Spetzler and Martin grade III, IV or V"}
• {"criterion_text":"- Whose symptoms are sufficiently severe to allow significant improvement with treatment: MoCA score ≤ 25 and/or ; NIHSS score ≥ 4 and/or ; Epilepsy Balance Score ≥ 2 and/or ; HIT-6 score ≥ 48"}
• {"criterion_text":"- With functional signs and symptoms not sequellar to a previous bleeding episode AND disabling (mRS>1)"}
• {"criterion_text":"- Ineligible for therapeutic intervention (endovascular or neurosurgery or radiosurgery)"}
• {"criterion_text":"- With normal bone marrow, liver and kidney function"}
• {"criterion_text":"- For women of childbearing potential: negative pregnancy test within 14 days prior to inclusion and effective contraception for up to 6 months after the end of treatment"}
• {"criterion_text":"- Fluency in the french language"}
• {"criterion_text":"- Having received informed consent to participate in the study"}

Exclusion criteria

• {"criterion_text":"- Known allergy to bevacizumab or an excipient"}
• {"criterion_text":"- Symptomatic peripheral vascular disease"}
• {"criterion_text":"- Vascular disease (aortic aneurysm, aortic dissection)"}
• {"criterion_text":"- Major surgery, open biopsy or significant traumatic lesion within 4 weeks prior to inclusion, or anticipation of need for major surgery during study period"}
• {"criterion_text":"- Biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to inclusion"}
• {"criterion_text":"- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of inclusion"}
• {"criterion_text":"- Significant unhealed wound, ulcer or bone fracture"}
• {"criterion_text":"- Thrombotic episode within 6 months prior to inclusion"}
• {"criterion_text":"- Atrial fibrillation"}
• {"criterion_text":"- Patient under legal protection"}
• {"criterion_text":"- Patient under legal protection"}
• {"criterion_text":"- Pregnant or breast-feeding women"}
• {"criterion_text":"- Hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanized antibodies"}
• {"criterion_text":"- Contraindication to cerebral MRI (claustrophobia, pacemaker or other implantable device contraindicating MRI)"}
• {"criterion_text":"- Absolute or relative contraindication to gadolinium injection (history of true allergic reaction or intolerance to gadobutrol, renal failure with creatinine clearance <15mL/min, pregnant or breast-feeding woman)"}
• {"criterion_text":"- Proteinuria ≥ 2+ on urine dipstick (patients with proteinuria ≥2+ on urine dipstick will need to have proteinuria ≤ 1g protein on 24-hour urine to be eligible)"}
• {"criterion_text":"- Uncontrolled hypertension (PAS >150 and/or PAD > 100 mmHg)"}
• {"criterion_text":"- History of hypertensive crisis or hypertensive encephalopathy"}
• {"criterion_text":"- Congestive heart failure (New York Heart Association Grade II or higher)"}
• {"criterion_text":"- Previous myocardial infarction or unstable angina in the preceding 12 months"}
• {"criterion_text":"- Patient with balanced blood pressure on quadritherapy"}

Primary endpoints

• {"endpoint_text":"- Comparison between the two arms of the proportion of patients showing at least one of the following improvements at 6 months: Increase of at least 5 points in MoCA score / Reduction of at least 4 points in NIHSS score / Improvement of at least one stage in epilepsy balance score - Reduction of at least 12 points on HIT-6 headache score","definition_or_measurement_approach":"Proportion of patients at 6 months meeting at least one component: increase ≥5 points in MoCA; reduction ≥4 points in NIHSS; improvement ≥1 stage in epilepsy balance score; reduction ≥12 points in HIT-6. Comparison between bevacizumab and placebo arms (Chi2 or Fisher's exact test)."}

Secondary endpoints

• {"endpoint_text":"- Increase of at least 5 points in MoCA score between M0 and M6","definition_or_measurement_approach":"Change in MoCA score from baseline (M0) to 6 months (M6); responder defined as increase ≥5 points."}
• {"endpoint_text":"- Reduction of at least 4 points in NIHSS score between M0 and M6","definition_or_measurement_approach":"Change in NIHSS score from baseline (M0) to 6 months (M6); responder defined as reduction ≥4 points."}
• {"endpoint_text":"- Reduction of at least one stage in epilepsy balance score between M0 and M6","definition_or_measurement_approach":"Change in epilepsy balance score from M0 to M6; responder defined as reduction of ≥1 stage."}
• {"endpoint_text":"- Reduction of at least 12 points in HIT-6 score between M0 and M6","definition_or_measurement_approach":"Change in HIT-6 headache score from M0 to M6; responder defined as reduction ≥12 points."}
• {"endpoint_text":"- Cerebral hemorrhage diagnosed by cerebral MRI at 6 months","definition_or_measurement_approach":"Occurrence of cerebral hemorrhage as diagnosed on brain MRI at 6 months."}
• {"endpoint_text":"- Percentage reduction in diameter of AVM drainage veins between brain MRI at M0 and M6","definition_or_measurement_approach":"Percent change in diameter of AVM drainage veins measured on brain MRI between M0 and M6."}
• {"endpoint_text":"- Evolution of peri-MAV edema on brain MRI between M0 and M6 according to the following categorization: improvement, stable or worsening","definition_or_measurement_approach":"Categorical assessment (improvement/stable/worsening) of peri-AVM edema on brain MRI between M0 and M6."}
• {"endpoint_text":"- Modified Rankin score (mRS) <2 at M6","definition_or_measurement_approach":"Proportion of patients with mRS <2 at 6 months."}
• {"endpoint_text":"- Change in modified Rankin score (mRS) between M0 and M6","definition_or_measurement_approach":"Change in mRS from baseline to 6 months."}
• {"endpoint_text":"- Change in EQ-5D-5L score from M0 to M6","definition_or_measurement_approach":"Change in EQ-5D-5L quality of life score from baseline to 6 months."}
• {"endpoint_text":"- All-cause mortality at 6 months","definition_or_measurement_approach":"All-cause death assessed at 6 months."}
• {"endpoint_text":"- Evolution of plasma VEGF concentration between M0 and M6","definition_or_measurement_approach":"Change in plasma VEGF concentration from baseline to 6 months."}
• {"endpoint_text":"- MoCA, HIT-6, NIHSS and epilepsy balance scores at 12 months","definition_or_measurement_approach":"Assessment of MoCA, HIT-6, NIHSS and epilepsy balance scores at month 12."}
• {"endpoint_text":"- mRS score at 12 months","definition_or_measurement_approach":"mRS assessed at 12 months."}
• {"endpoint_text":"- EQ-5D-5L score at 12 months","definition_or_measurement_approach":"EQ-5D-5L assessed at 12 months."}
• {"endpoint_text":"- Rate of occurrence of cerebral haemorrhage diagnosed by cerebral MRI at 12 months","definition_or_measurement_approach":"Occurrence of cerebral haemorrhage on brain MRI by 12 months."}
• {"endpoint_text":"- Rate of occurrence of adverse events at 12 months","definition_or_measurement_approach":"Rate of adverse events recorded up to 12 months."}

France

Earliest CTIS Part Ii Submission Date

05-02-2024

Latest Decision Or Authorization Date

27-06-2025

Processing Time Days

508

Number Of Sites

1

Number Of Participants

54

Primary sponsor

Full Name

Hopital Fondation Adolphe De Rothschild

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"Ministry of solidarity and health","duties_or_roles":"Source of monetary support (funding)","organisation_type":"Government / Funder"}