Table 2.

RCTs included in the systematic literature search.

Study	Period	Country	Number of subjects IG/CG	Inclusion/exclusion - Criteria	Control group(s)	MMAE Time	MMAE technique	Endpoints	Results	Sponsor
Ng et al. − 2020	04/2018-10/2018	France Single-center	Initial 21 Final 19/22 Median age 77 and 75 years, respectively, 56% ♂	Inclusion: > 18 years, cSDH requiring surgery Exclusion: previous cSDH surgery, cSDH width < 10 mm or > 50% acute component, underlying pathology (cyst, vascular), < 6 months life expectancy	Surgery (drill hole/craniotomy)	Additive during the same hospital stay	PVA 150–250 μm (coils if necessary) 100% under sedation n = 1 technically unsuccessful due to tortuous vessels	1.cSDH resorption within 90 days on CT	Lower cSDH volume in the IG (mean difference 17.5 mL, 95% CI 3.87–31.16, p = 0.015)	No funding declared
								2. Recurrence (persistent cSDH with remaining or new symptoms)	One recurrence in each group
								3. Safety	n = 1 death in the CG due to pneumonia, no MMAE-associated complications
Davies et al. 2024 – “EMBOLISE"	12/2020-08/2023	USA Multicenter in 39 centers	Initial 197/203 Final 167/180 Median age 73 and 71 years 73% ♂	Inclusion: 18–90 years, subacute/chronic SDH requiring surgery Exclusion: Life expectancy < 1 year, mRS ≥ 4 before cSDH, Markwalder Grading Scale ≥ 3	Surgery (drill hole/craniotomy)	Additive pre-surgery (58%) or post-surgery (42%) within 48 h after randomization	Open-label Onyx 79% under general anesthesia 93.9% technically successful n = 10 Anastomotic failures n = 1 coiling n = 53 (13.2%) lost to follow-up n = 1 refused MMAE	1. recurrence or progression with indication for surgery within 90 days	Fewer recurrence surgeries in the IG n = 8 (4.1%) in IG n = 23 (11.3%) in CG (relative risk 0.36; 95% CI 0.11–0.80, p = 0.008; NNT 14)	Industrial (Medtronic)
								2. Worsening mRS within 90 days	11.9% neurological deterioration in the IG, 9.8% in the CG
								3. Mortality within 90 days	n = 10 (5.1%) in the IG n = 6 (3.0%) in the CG
								4. SAE within 180 days	n = 4 (2.0%) in the IG after 30 days (n = 2 strokes in MMAE, not caused by embolism)
								5. Rehospitalization, change in hematoma volume and width, midline shift within 90 days	Similar in both groups
Fiorella et al. − 2025 STEM	11/2020-05/2023	USA, France, Sweden Multicenter in 32 centers	Initial 149 Final 120/129 Median age 73 70% ♂	Inclusion: symptomatic cSDH > 10 mm width Exclusion: mRS > 1 before cSDH, craniotomy	surgery (burr hole/port evacuation) n = 189 or Conservative therapy n = 121	Additive pre-surgery or additive to conservative therapy within 24 h after randomization	Open-label Squid 100% under general anesthesia 99% technically successful n = 1 No embolization due to anatomical causes n = 1 partial embolization plus coiling	1. recurrence or residual findings > 10 mm after 180 days; Reoperation or rescue surgery within 180 days; Disabling stroke/myocardial infarction/death due to neurological causes within 180 days	Fewer primary endpoints in the IG n = 19 (16%) in IG, n = 47 (36%) in CG (OR 0.36; 95% CI 0.20 to 0.66; p = 0.001) Especially in the conservatively treated subgroup benefit of additive MMAE (19% in the IG and 56% in the CG) Most frequent primary event Recurrence/rescue surgery, n = 51 (20%)	Industrial (BALT)
								2. Disabling stroke or death within 30 days	No difference n = 4 (3%) in the IG n = 5 (3%) in the CG
								3. mRS after 180 days	No significant difference
								4. AE/SAE due to MMAE	None
Debs et al. − 2024	03/2019-11/2022	USA Mono-centric	Initial 19 Final 17/18 Median age 66 and 71 years, respectively 66% ♂	Inclusion: 18–90 years, cSDH requiring surgery, mRS < 5 Exclusion: mRS > 4, Creatinine > 1.8, Coagulation disorder, Coagulopathy, Pregnancy	Surgery (drill hole or mini-craniotomy)	Additive within 72 h post-surgery	Onyx 100% under general anesthesia	1. Neurological outcome 4–6 weeks after discharge (or earlier in case of deterioration)	No difference at discharge, but deterioration in the control group at follow-up (33% vs. 71%, RR 0.44, p = 0.03, NNT 2.6).	No funding declared
								2. Medical resource utilization until complete resolution of cSDH	More repeat surgeries in the CG n = 1 (6%) in IG n = 7 (39%) in CG (p = 0.02, NNT 3) Longer hospital stay in the CG (p = 0.02) More imaging in the CG (p = 0.01) Faster resolution in IG (⌀ 39 d in IG and 205 d in CG, p = 0.02)
Liu et al. − 2024 – “MAGIC-MT"	03/2021-05/2023	China Multicenter in 31 centers	Initial 360/362 Final 346/345 Median age 69 years, 82.5% ♂	Inclusion: > 18 years, symptomatic non-acute SDH with space-occupying effect, mRS < 3 Exclusion: Craniotomy, bilateral SDH with unclear etiology of symptoms, life expectancy < 1 year, mRS > 2 before onset of symptoms, SDH recurrence	Surgery (drill hole) in 78% or Conservative therapy in 22%	Additive pre-surgery or additive to conservative therapy	Open-label Onyx Local anesthesia or general anesthesia In 99.6% pre-op	1. Symptomatic SDH recurrence (width > 10 mm) or progression (increase > 3 mm from baseline/post-op) or re-op within 90 days	Fewer primary endpoints in the IG n = 24 (6.7%) in the IG n = 36 (9.9%) in the CG (− 3.3%; 95% confidence interval, − 7.4–0.8%; p = 0.10) Especially in the conservatively treated subgroup benefit of additive MMAE	Partially industrial (Covidien/ Medtronic)
								2. Late recurrence after 1 year, successful MMAE in DSA, change in hematoma thickness or volume after 90 days, change in midline after 90 days, change in mRS between 90 days and 1 year, quality of life after 90 days and 1 year, length of hospital stay, re-hospitalizations, hospital costs, deaths in 1 year	No difference between the groups
								3. SAE within 90 days and 1 year, intervention-associated complications within 30 days	SAE less frequent in the IG than in the CG (6.7% vs. 11.6%) Mortality lower in the IG (0.6% vs. 2.2%) Intervention-associated complications: n = 1 facial nerve palsy and n = 2 KM allergy
Lam et al. − 2023	04/2021-09/2022	Australia Multicenter in 2 centers	Initial 17 Final 16/16 Median age 64 and 72 years, respectively 75% ♂ in IG, 58% ♂ in KG	Inclusion: > 18 years, cSDH requiring surgery > 10 mm width Exclusion: underlying cause (malformation, cyst)	Surgery (drill hole/craniotomy)	Additive post-op during the same hospital stay	Qnyx-18, Squid-12, Phil 25%, NBCA with 25% Lipiodol 100% under general anesthesia	1. recurrence requiring surgery (persistent or new cSDH with persistent or new symptoms)	No recurrence in the IG with n = 3 (15.8%) recurrences in the CG (p = 0.234)	Not industrial (Life Health Care Group)
								2. Residual hematoma width after 6 weeks or 3 months	No significant difference between the groups
								3. mRS after 6 weeks or 3 months	Significantly lower mRS (0–1) after 3 months in the IG (100% vs. 53%, p = 0.018).
								4. AE/SAE	No MMAE-associated complications
Shotar et al. − 2025 – “EMPROTECT"	07/2021-03/2023	France Multicenter in 12 centers	Initial 171/171 Final 162/157 Median age 77 80% ♂	Inclusion: > 18 years with recurrent cSDH or high risk of recurrence Exclusion: mRS > 4 prior to cSDH, life expectancy < 6 months, renal failure, pregnancy, contrast medium allergy	Surgery (drill hole)	Additive post-op within 7 days	Embosphere-TAGM 300–500 μm n = 13 No embolization at anastomoses n = 4 Frustrated catheterization in cases of difficult access n = 2 No embolization in severe atheromatosis n = 5 refused MMAE	1. cSDH recurrence after 6 months (> 10 mm width, > 5 mm midline shift or symptoms, reoperation, rehospitalization)	Fewer cSDH recurrences in IG n = 24 (14.8%) in the IG n = 33 (21%) in the CG (OR 0.64, 95% CI 0.36–1.14, p = 0.13)	No funding declared
								2. Recurrence surgery rate after 6 months, mRS ≥ 4 after 1 and 6 months, mortality after 1 and 6 months	Fewer repeat surgeries in the IG n = 7 (4.3%) in the IG n = 13 (8.3%) in the CG (p = 0.14) No significant differences in mRS or mortality
								3. AE/SAE due to MMAE	n = 1 (0.6%) MCA occlusion during MMAE n = 2 (1.2%) transient hemiparesis or aphasia n = 1 (0.6%) Headache
Manzato et al. − 2025	08/2021-08/2024	Brazil Single-center	Initial 33/43 Final 27/38 Median age 73 and 74 years 84% ♂ in IG 75% ♂ in CG	Inclusion: > 18 years, cSDH requiring surgery, Exclusion: acute SDH (> 50% fresh components), previous intervention for cSDH, underlying disease	Surgery (drill hole)	Additive post-op within 7 days	NBCA with 14% lipiodol 100% general anesthesia n = 1 technically not possible	1. Recurrence rate within 90 days (increase in cSDH with symptoms and need for surgery)	Fewer recurrences in the IG n = 1 (4.2%) in the IG n = 4 (12.5%) in the CG (p = 0.379)	No funding declared
								2. 90-day mortality	Lower mortality in the IG n = 2 (6.1%) in the GI n = 5 (11.6%) in the CG (p = 0.434)
								3. AE/SAE, length of hospital stay	More frequent complications during hospitalization in CG (p = 0.060). n = 1 SAE due to MMAE (pseudoaneurysm of the AFC) Similar length of hospitalisation in the IG and CG.

IG – intervention group, CG – control group, AE/SAE – (serious) adverse events (complications), SDH – subdural hematoma, AFC – common femoral artery, MCA – middle cerebral artery, CM – contrast agent, NBCA – n-butyl cyanoacrylate.