Middle Cerebral Artery Occlusion With Cerebral InfarctionAGAINSTNCT05860855
The AGAINST Protocol: Augmentative Craniotomy in Stroke
A study testing Augmentative craniotomy and Decompressive craniotomy in people with Middle Cerebral Artery Occlusion With Cerebral Infarction, run by University of Roma La Sapienza.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Middle Cerebral Artery Occlusion With Cerebral Infarction
- What is being tested?
- Augmentative craniotomy and Decompressive craniotomy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- No sites listed yet
- Study dates
- Jun 2023to Oct 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- - presence of concomitant or associated brain lesion
- presence of concomitant comorbidities or other clear contraindications for treatment
- participation in any other interventional trial
Trial locations and contacts
No sites are listed yet.
About this study
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
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.
Read the 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.
- Being tested
- Augmentative craniotomy, Decompressive craniotomy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Augmentative craniotomyProcedure or surgery
Expansion of the skull
Decompressive craniotomyProcedure or surgery
Standard hemicraniectomy
| Study group | Role | What they receive |
|---|---|---|
| Decompressive hemicraniectomy | Active comparator | 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. Receives: Procedure: Decompressive craniotomy |
| Augmentative craniotomy | Experimental | 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. Receives: Procedure: Augmentative craniotomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in functional and neurological status
Modified Rankin score(mRS) ranges from 0 to 6. Lower points represent better outcomes
Measured: From recruitment to 12 months
Changes in quality of life
36-item short form survey (SF-36) ranges from 0 to 100. Lower points represent worse outcomes
Measured: From recruitment to 12 months
Changes in functional and neurological status
Barthel index ranges from 0 to 100. Lower points represent worse outcomes
Measured: From recruitment to 12 months
Changes in functional and neurological status
National Institute of Health Stroke Scale (NIHSS), ranges from 0 to 42. Lower point represent better outcomes
Measured: From recruitment to 12 months
Changes in quality of life
EuroQol 5D (EQ-5D) ranges from 0 to 100. Lower point represent worse outcomes
Measured: From recruitment to 12 months
Secondary outcomes (1)
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
Measured: From recruitment to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2023
- Study startJun 2023 (estimated)
- Primary completionOct 2024 (estimated)
- Study completionOct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Middle Cerebral Artery Occlusion With Cerebral InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Luigi Valentino Berra, University of Roma La Sapienza
- Investigators
- Luigi Valentino Berra, Principal investigator, University of Roma La Sapienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05860855
- Sponsor's protocol ID
- AGAINST 001
- Acronym
- AGAINST
- Status last verified
- May 2023
- First submitted
- 21 Jun 2022
- Last updated
- 16 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05860855
- Acronym / sponsor ID
- AGAINST / AGAINST 001
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- Jun 2023 (estimated)
- Primary completion
- Oct 2024 (estimated)
- Study completion
- Oct 2024 (estimated)
- First posted
- 16 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Decompressive hemicraniectomy | Active comparator | Procedure: Decompressive craniotomyThe 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. |
| Augmentative craniotomy | Experimental | Procedure: Augmentative craniotomySurgical 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (3 listed)
- - presence of concomitant or associated brain lesion
- presence of concomitant comorbidities or other clear contraindications for treatment
- participation in any other interventional trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Augmentative craniotomyExpansion of the skull | Procedure or surgery | Augmentative craniotomy |
| Decompressive craniotomyStandard hemicraniectomy | Procedure or surgery | Decompressive hemicraniectomy |
Primary outcome
Changes in functional and neurological status
Time frame: From recruitment to 12 months
Modified Rankin score(mRS) ranges from 0 to 6. Lower points represent better outcomes
Changes in quality of life
Time frame: From recruitment to 12 months
36-item short form survey (SF-36) ranges from 0 to 100. Lower points represent worse outcomes
Changes in functional and neurological status
Time frame: From recruitment to 12 months
Barthel index ranges from 0 to 100. Lower points represent worse outcomes
Changes in functional and neurological status
Time frame: From recruitment to 12 months
National Institute of Health Stroke Scale (NIHSS), ranges from 0 to 42. Lower point represent better outcomes
Changes in quality of life
Time frame: From recruitment to 12 months
EuroQol 5D (EQ-5D) ranges from 0 to 100. Lower point represent worse outcomes
1 secondary outcome
surgical complications
Time frame: From recruitment to 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2023.
- Individual participant dataSharing planned: Yes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luigi Valentino Berra principal investigator
University of Roma La Sapienza
Questions about this trial
What is this clinical trial studying?
A study testing Augmentative craniotomy and Decompressive craniotomy in people with Middle Cerebral Artery Occlusion With Cerebral Infarction, run by University of Roma La Sapienza.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 May 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Luigi Valentino Berra, M.D. (+393491475626, l.berra@policlinicoumberto1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in functional and neurological status (time frame: From recruitment to 12 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2023.