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The AGAINST Protocol: Augmentative Craniotomy in Stroke (AGAINST)

Primary Purpose

Middle Cerebral Artery Occlusion With Cerebral Infarction

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Augmentative craniotomy
Decompressive craniotomy
Sponsored by
University of Roma La Sapienza
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Middle Cerebral Artery Occlusion With Cerebral Infarction

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Only MCA ischemic strokes have been considered, with no distinctions between the execution of precedent treatment (thrombolysis and/or thrombectomy) Patients' age <75 years old. NIHSS >1a, >14 for right sided lesions, >15 for left sided lesions Symptoms onset <48 hours before surgery or conservative treatment Neuroradiological findings: unilateral ischemic infarction of at least 1/3 of MCA territory is involved. Ischemic core volume>140ml. Hypodensity on head CT within the first 6 hours of stroke onset involving one-third or more of the MCA territory, early midline shift, and magnetic resonance imaging diffusion-weighted imaging volume within 6 hours ≥80 mL. informed consent by the patient him/herself, his/her legal representative, adjudication by a legally competent judge, or by an independent physician Exclusion Criteria: - presence of concomitant or associated brain lesion presence of concomitant comorbidities or other clear contraindications for treatment participation in any other interventional trial

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    Decompressive hemicraniectomy

    Augmentative craniotomy

    Arm Description

    The procedure of hemicraniectomy is performed in the same way as the augmentative craniotomy from skin incision to dural augmentation. Then, the myo-cutaneous flaps are reapproximated and sealed and the operculum is secured. Then, cranioplasty with autologous bone will be performed within 6-months after the hemicraniectomy.

    Surgical incision according to Kempe is performed to obtain a better vascularization of the myo-cutaneous flap, to guarantee a larger surgical exposition and to facilitate the closure. The incision starts from "widow's peak" and arrives 1 cm upon the inion and it is performed parallel to the midline, 3 cm from it. Then a second incision is performed from the center of the first one and it will be extended inferiorly to the tragus. Burr holes will be performed in the frontal-basal region (keyhole), temporal region and superior and medial to the inion. Supplementary burr holes can be performed. Then, a large frontal-temporal-parietal-occipital craniotomy not smaller than 12x15 cm is performed. Then dural augmentation is performed with the positioning of a dural patch. The operculum is repositioned through the application of 5 titanium clamps secured with screws 1 cm above the margin of the craniotomy. The myo-cutaneous flaps are reapproximated and sealed.

    Outcomes

    Primary Outcome Measures

    Changes in functional and neurological status
    Modified Rankin score(mRS) ranges from 0 to 6. Lower points represent better outcomes
    Changes in quality of life
    36-item short form survey (SF-36) ranges from 0 to 100. Lower points represent worse outcomes
    Changes in functional and neurological status
    Barthel index ranges from 0 to 100. Lower points represent worse outcomes
    Changes in functional and neurological status
    National Institute of Health Stroke Scale (NIHSS), ranges from 0 to 42. Lower point represent better outcomes
    Changes in quality of life
    EuroQol 5D (EQ-5D) ranges from 0 to 100. Lower point represent worse outcomes

    Secondary Outcome Measures

    surgical complications
    haemorrhage requiring blood transfusions, anaesthesia-related incidents, pharmacological treatment, impaired wound healing or wound infection, liquor fistula, hygroma, or any other secondary complication leading to prolongation of hospitalization or rehospitalization. The incidence of hydrocephalus and sunken flap syndrome

    Full Information

    First Posted
    June 21, 2022
    Last Updated
    May 11, 2023
    Sponsor
    University of Roma La Sapienza
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05860855
    Brief Title
    The AGAINST Protocol: Augmentative Craniotomy in Stroke
    Acronym
    AGAINST
    Official Title
    The AGAINST Protocol: Augmentative Craniotomy in Stroke: a Prospective, Randomized, Controlled, Multicentre, Comparative Trial on Decompressive Craniectomy and Augmentative Craniotomy in Malignant Middle Cerebral Infarction
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 2023 (Anticipated)
    Primary Completion Date
    October 2024 (Anticipated)
    Study Completion Date
    October 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Roma La Sapienza

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Malignant Middle Cerebral Artery (MCA) infarction is a term used for the severe clinical and neurological hemispheric syndrome caused by ischemic occlusion of the proximal tract of MCA and it is observed in near the 10% of all ischemic strokes.In order to prevent the severe consequences caused by malignant MCA infarction, decompressive hemicraniectomy has been proposed as early intervention against the expected clinical worsening due to endocranial hypertension and several trials demonstrated how it positively affects the mortality and morbidity rates compared to conservative management. However, patients undergoing decompressive hemicraniectomy generally encounter other kinds of complications, related to the consequences of the surgical procedure. With the intent of reducing these complications, alternative decompression techniques have been proposed, such as hinge or floating craniectomy or augmentative craniotomy, in which the bony operculum is left in place. These alternative methods of cranial decompression have been shown to have similar efficacy to standard craniectomy, but comparative trials have never been conducted.In the present protocol, the investigators present a study design that compares the standard decompressive hemicraniectomy to a novel technique of augmentative craniotomy. The rationale of the study is to maintain the important advantages related to brain decompression in malignant MCA infarction while avoiding the complications related to the surgical procedure of hemicraniectomy.
    Detailed Description
    AGAINST is a prospective, randomised, controlled, open, multicentre, two-armed, comparative trial. Patients are randomised 1:1 to either treatment with hemicraniectomy or with augmentative craniotomy. Complete blinding is virtually impossible both for treating physicians and patients due to visible aesthetic differences between the two groups. All participating centers dispose of 24/h per day neurosurgical facilities. Ethical boards of each participating center approved the present trial protocol. The enrollment will stop as soon as statistical difference between two groups would be reached. The study design of the present clinical trial protocol adhere to the SPIRIT and CONSORT guidelines. Treatment protocol Patients who pass the screening of inclusion and criteria will be considered suitable for the enrollment in the study. After medical evaluation and neuroimaging, written informed consent will be obtain before enrolling the patient in the study. Then, randomization is performed online (trough http//:randomizer.at) and, if the online randomization fails, patients will be randomized through a sealed envelope system managed by a 24-h/7-day phone service. Consequentially, the patient is assigned to one of the following groups of treatment: Group I, augmentative craniotomy; Group 2, decompressive hemicraniectomy. Surgical treatment will be performed not later than 48 hours after symptoms onset and not later than 6 hours after randomization. The allocation ratio between the two groups is 1:1. Augmentative craniotomy Surgical incision according to "Kempe" is performed to obtain a better vascularization of the myo-cutaneous flap, to guarantee a larger surgical exposition and to facilitate the closure. The incision starts from "widow's peak" and arrives 1 cm upon the inion and it is performed parallel to the midline, 3 cm from it. If exposition of the keyhole is requested, frontal incision line can be extended 2 cm along the ipsilateral hairline. Then a second incision is performed from the center of the first one and it will be extended inferiorly to the tragus. Burr holes will be performed in the frontal-basal region (keyhole), temporal region and superior and medial to the inion. Supplementary burr holes can be performed the superior margin of the skin incision. Then, a large frontal-temporal-parietal-occipital craniotomy not smaller than 12x15 cm (area >140 cm2) is performed, according to Brain Trauma Foundation guidelines12. Then the dura is opened in a "star" shape and dural augmentation is performed with the positioning of a dural patch. The operculum is repositioned through the application of 5 titanium clamps secured with screws 1 cm above the margin of the craniotomy. The myo-cutaneous flaps are reapproximated and sealed. Decompressive craniectomy The procedure of hemicraniectomy is performed in the same way as the augmentative craniotomy from skin incision to dural augmentation. Then, the myo-cutaneous flaps are reapproximated and sealed and the operculum is secured. Then, cranioplasty with autologous bone will be performed within 6-months after the hemicraniectomy. Data collection, statistical analysis and duration For patients in both groups at baseline a complete clinical and neurological evaluation will be performed an all the following data will be collected: age, sex, weight, NIHSS, modified Rankin Score (MRS), time and date onset of symptoms, Glasgow Coma Scale (GCS), Barthel Index, neuroimaging data (CT and MRI scans showing timing of the ischemic stroke, ischemic core infarction volume), comorbidities. At 6- and 12-months a complete medical and neurological evaluation will be performed along with MRI scans. Data related to primary and secondary endpoints will be registered: NIHSS, MRS, Barthel Index, SF-36, EuroQoL 5D, presence of sunken flap syndrome, presence of hydrocephalus.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Middle Cerebral Artery Occlusion With Cerebral Infarction

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    Participant
    Allocation
    Randomized
    Enrollment
    70 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Decompressive hemicraniectomy
    Arm Type
    Active Comparator
    Arm Description
    The procedure of hemicraniectomy is performed in the same way as the augmentative craniotomy from skin incision to dural augmentation. Then, the myo-cutaneous flaps are reapproximated and sealed and the operculum is secured. Then, cranioplasty with autologous bone will be performed within 6-months after the hemicraniectomy.
    Arm Title
    Augmentative craniotomy
    Arm Type
    Experimental
    Arm Description
    Surgical incision according to Kempe is performed to obtain a better vascularization of the myo-cutaneous flap, to guarantee a larger surgical exposition and to facilitate the closure. The incision starts from "widow's peak" and arrives 1 cm upon the inion and it is performed parallel to the midline, 3 cm from it. Then a second incision is performed from the center of the first one and it will be extended inferiorly to the tragus. Burr holes will be performed in the frontal-basal region (keyhole), temporal region and superior and medial to the inion. Supplementary burr holes can be performed. Then, a large frontal-temporal-parietal-occipital craniotomy not smaller than 12x15 cm is performed. Then dural augmentation is performed with the positioning of a dural patch. The operculum is repositioned through the application of 5 titanium clamps secured with screws 1 cm above the margin of the craniotomy. The myo-cutaneous flaps are reapproximated and sealed.
    Intervention Type
    Procedure
    Intervention Name(s)
    Augmentative craniotomy
    Intervention Description
    Expansion of the skull
    Intervention Type
    Procedure
    Intervention Name(s)
    Decompressive craniotomy
    Intervention Description
    Standard hemicraniectomy
    Primary Outcome Measure Information:
    Title
    Changes in functional and neurological status
    Description
    Modified Rankin score(mRS) ranges from 0 to 6. Lower points represent better outcomes
    Time Frame
    From recruitment to 12 months
    Title
    Changes in quality of life
    Description
    36-item short form survey (SF-36) ranges from 0 to 100. Lower points represent worse outcomes
    Time Frame
    From recruitment to 12 months
    Title
    Changes in functional and neurological status
    Description
    Barthel index ranges from 0 to 100. Lower points represent worse outcomes
    Time Frame
    From recruitment to 12 months
    Title
    Changes in functional and neurological status
    Description
    National Institute of Health Stroke Scale (NIHSS), ranges from 0 to 42. Lower point represent better outcomes
    Time Frame
    From recruitment to 12 months
    Title
    Changes in quality of life
    Description
    EuroQol 5D (EQ-5D) ranges from 0 to 100. Lower point represent worse outcomes
    Time Frame
    From recruitment to 12 months
    Secondary Outcome Measure Information:
    Title
    surgical complications
    Description
    haemorrhage requiring blood transfusions, anaesthesia-related incidents, pharmacological treatment, impaired wound healing or wound infection, liquor fistula, hygroma, or any other secondary complication leading to prolongation of hospitalization or rehospitalization. The incidence of hydrocephalus and sunken flap syndrome
    Time Frame
    From recruitment to 12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Only MCA ischemic strokes have been considered, with no distinctions between the execution of precedent treatment (thrombolysis and/or thrombectomy) Patients' age <75 years old. NIHSS >1a, >14 for right sided lesions, >15 for left sided lesions Symptoms onset <48 hours before surgery or conservative treatment Neuroradiological findings: unilateral ischemic infarction of at least 1/3 of MCA territory is involved. Ischemic core volume>140ml. Hypodensity on head CT within the first 6 hours of stroke onset involving one-third or more of the MCA territory, early midline shift, and magnetic resonance imaging diffusion-weighted imaging volume within 6 hours ≥80 mL. informed consent by the patient him/herself, his/her legal representative, adjudication by a legally competent judge, or by an independent physician Exclusion Criteria: - presence of concomitant or associated brain lesion presence of concomitant comorbidities or other clear contraindications for treatment participation in any other interventional trial
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Luigi Valentino Berra, M.D.
    Phone
    +393491475626
    Email
    l.berra@policlinicoumberto1.it
    First Name & Middle Initial & Last Name or Official Title & Degree
    Mauro Palmieri, M.D.
    Phone
    +393461316999
    Email
    mauro.palmieri@uniroma1.it
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Luigi Valentino Berra
    Organizational Affiliation
    University of Roma La Sapienza
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes

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    The AGAINST Protocol: Augmentative Craniotomy in Stroke

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