Landmark trial for ICH
Your credits are exhausted. You can purchase a top-up or subscribe to a plan to continue using Orris. If you're already subscribed, your daily credits will reset tomorrow.
Important landmark trial for IcH
Reading File
Finding Sources
Searching PubMed
"intracerebral hemorrhage"[MeSH Terms]
Searching the Web
2022 AHA guideline spontaneous intracerebral hemorrhage landmark trials INTERACT2 ATACH II STICH MISTIE TICH-2
For spontaneous intracerebral hemorrhage (ICH), these are the highest-yield landmark trials to know:
| Clinical question | Landmark trial | Main takeaway |
|---|---|---|
| Acute BP lowering | INTERACT-2 (2013) | Targeting SBP <140 mmHg was safe and produced a modest improvement in functional outcome distribution compared with <180 mmHg. |
| ATACH-II (2016) | More aggressive BP lowering to 110-139 mmHg did not improve death/disability and increased renal adverse events. Avoid pushing SBP too low. | |
| INTERACT-3 (2023) | A bundle of early care, including BP reduction, anticoagulant reversal, glucose and temperature management, improved 6-month functional outcomes. | |
| Open surgical evacuation | STICH (2005) | Early craniotomy showed no overall benefit over initial conservative treatment in supratentorial ICH. |
| STICH-II (2013) | In selected superficial lobar ICH without IVH, early surgery did not significantly improve functional outcome, though it may offer a small survival benefit. | |
| Minimally invasive evacuation | MISTIE III (2019) | Catheter evacuation plus alteplase did not improve the primary 1-year functional outcome overall. Better clot reduction, particularly residual volume ≤15 mL, was associated with better outcomes. |
| ENRICH (2023/2024) | Early trans-sulcal minimally invasive evacuation improved 180-day functional outcome overall, with benefit largely in lobar ICH, not deep basal-ganglia hemorrhage. | |
| Tranexamic acid | TICH-2 (2018) | TXA did not improve 90-day functional outcome, despite reducing early death and hematoma expansion signals. |
| Platelet transfusion in antiplatelet-associated ICH | PATCH (2016) | Platelet transfusion was harmful in spontaneous ICH patients taking antiplatelet drugs who were not undergoing emergency neurosurgery. |
| Warfarin reversal | INCH (2016) | Four-factor PCC reversed INR more rapidly and effectively than FFP in vitamin K antagonist-associated ICH. |
| Factor Xa inhibitor reversal | ANNEXA-I (2024) | Andexanet alfa produced better hemostatic efficacy than usual care, but caused more thrombotic events; functional benefit remains less clear. |
| Restarting antiplatelets after ICH | RESTART (2019) | Restarting antiplatelet therapy after ICH did not show an increased risk of recurrent ICH. |
Most commonly asked in exams
- STICH: surgery versus conservative management
- INTERACT-2 and ATACH-II: blood-pressure targets
- MISTIE III: minimally invasive evacuation plus thrombolysis
- PATCH: do not give platelets routinely for antiplatelet-associated spontaneous ICH
- TICH-2: tranexamic acid not beneficial for 90-day functional outcome
- RESTART: antiplatelet restart after ICH
A useful one-line summary is:
STICH showed no routine benefit of open surgery; INTERACT-2 supported cautious SBP lowering toward 140 mmHg; ATACH-II showed overly intensive BP reduction is not beneficial; PATCH showed platelet transfusion can harm; MISTIE III was neutral overall.
The 2022 AHA/ASA ICH guideline remains a useful framework for applying these trial findings clinically.
Find the latest guidelines for applying these trials
Reading File
Searching the Web
latest guideline spontaneous intracerebral haemorrhage 2025 ESO EANS guideline blood pressure reversal surgery antithrombotic
Searching PubMed
"intracerebral hemorrhage"[MeSH Terms] AND guideline
Finding Sources
Reading Web Page
https://journals.sagepub.com/doi/10.1177/23969873251340815
Reading Article
PMID: 40401775
Reading Article
PMID: 35579034
Reading Article
PMID: 39707127
Reading Web Page
https://pmc.ncbi.nlm.nih.gov/articles/PMC12098356/
Searching PubMed
"intracerebral hemorrhage"[MeSH Terms] AND "blood pressure"
Finding Sources
Current guideline hierarchy for spontaneous ICH
- Most current comprehensive guideline: 2025 ESO-EANS guideline for spontaneous ICH, published May 2025 (Steiner et al., 2025).
- Current US comprehensive guidance: 2022 AHA/ASA ICH guideline (Greenberg et al., 2022).
- Newer BP-specific US update: 2025 AHA/ACC hypertension guideline, which updates practical acute ICH BP advice (2025 AHA/ACC BP guideline).
Applying the landmark trials at the bedside
| Trial(s) | Current application in guidelines |
|---|---|
| INTERACT-2, ATACH-II, INTERACT-3 | For mild-to-moderate spontaneous ICH, presenting early with SBP 150-220 mmHg, lower SBP promptly and smoothly toward 140 mmHg. AHA/ASA specifies a practical maintenance range of 130-150 mmHg and advises against reducing SBP below 130 mmHg. Avoid abrupt drops and BP variability. The 2025 ESO-EANS guideline supports SBP <140 mmHg within 6 hours in minor-to-moderate ICH, particularly hematoma volume <30 mL. |
| STICH and STICH-II | Do not offer routine early open craniotomy to all supratentorial ICH patients. Functional benefit is uncertain. Consider evacuation as a potentially life-saving intervention for deterioration, significant mass effect/midline shift, or refractory intracranial pressure, with neurosurgical input. Superficial lobar hematoma is the subgroup most plausibly considered. |
| MISTIE III and ENRICH | Minimally invasive hematoma evacuation is no longer simply “experimental,” but selection matters. It may reduce mortality in selected supratentorial ICH, while functional benefit is less certain overall. ENRICH supports early minimally invasive surgery mainly for lobar ICH, not deep basal ganglia hemorrhage. Refer suitable patients early to a center with the technique and trial-like expertise. |
| TICH-2 | Do not use tranexamic acid routinely to improve 90-day functional outcome in spontaneous ICH. It can reduce hematoma expansion signals, but guideline-level evidence does not establish a meaningful functional benefit. Use should generally be restricted to protocols or selected specialist decisions. |
| PATCH | Do not give platelet transfusion routinely to patients with spontaneous ICH taking aspirin or other antiplatelet therapy if they are not undergoing emergency neurosurgery. It worsened outcomes in PATCH. For urgent surgery, management should be individualized with neurosurgery and hematology. |
| INCH | For warfarin-associated ICH, reverse immediately with 4-factor PCC plus IV vitamin K. PCC is preferred over FFP because it corrects INR much faster. Do not wait for repeat imaging or INR results if the history is convincing. |
| ANNEXA-I | For factor Xa inhibitor-associated ICH, andexanet alfa is an option when available and appropriate, because it improves hemostatic efficacy; balance this against increased thrombotic events and uncertain net functional benefit. If unavailable, 4-factor PCC remains widely used as an alternative, according to local protocol. |
| RESTART | Restarting antiplatelet therapy after ICH can be considered when the ischemic indication is strong, after individualized assessment of recurrence risk, location/cause of ICH, and BP control. It is not automatically required, nor automatically contraindicated. |
Practical acute ICH order set
1. First hours
- Admit to a stroke unit or neurocritical care setting.
- Confirm with noncontrast CT, assess hematoma volume, location, intraventricular extension, hydrocephalus, and expansion risk.
- For eligible patients with SBP 150-220 mmHg: use titratable IV treatment to reach around 140 mmHg, then maintain 130-150 mmHg.
- Do not produce hypotension, large SBP variability, or SBP <130 mmHg.
- Reverse anticoagulation immediately.
The 2025 ESO-EANS guideline emphasizes early BP treatment, ideally within 2 hours, reduction of BP variability, anticoagulant reversal, stroke-unit care, and multidisciplinary care bundles. It supports a care-bundle approach informed by INTERACT-3. The bundle included SBP <140 mmHg, rapid warfarin reversal, temperature management, and glucose management, and was associated with better functional outcome in the trial (ESO-EANS guidance).
2. Hemostatic treatment
- Warfarin: 4F-PCC + IV vitamin K.
- Dabigatran: idarucizumab.
- Apixaban/rivaroxaban/edoxaban: consider andexanet alfa where indicated and available; otherwise use institutional PCC-based reversal protocol.
- Antiplatelet-associated ICH: no routine platelet transfusion unless a specialist team believes urgent surgery changes the balance.
- TXA/rFVIIa: not routine treatments for unselected spontaneous ICH.
3. Neurosurgical pathway
Obtain early neurosurgical consultation for:
- Cerebellar ICH, especially with deterioration, brainstem compression, hydrocephalus, or large volume.
- Obstructive hydrocephalus or substantial intraventricular hemorrhage, where external ventricular drainage may be indicated.
- Lobar superficial ICH with mass effect or clinical deterioration.
- Potential minimally invasive surgery candidates, particularly early lobar ICH in experienced centers.
4. What not to do routinely
- Routine open craniotomy for all supratentorial ICH.
- Routine platelet transfusion for aspirin-associated ICH without planned emergency surgery.
- Routine prophylactic antiseizure medication in a patient without clinical or electrographic seizures.
- Routine prophylactic corticosteroids.
- Routine TXA solely to improve long-term functional outcome.
- Early irreversible limitation-of-care decisions based only on an ICH severity score.
For seizures, the 2025 Neurocritical Care Society guideline suggests avoiding prophylactic antiseizure medication in adults with acute nontraumatic ICH without seizures. If medication is used in a specific circumstance, levetiracetam is preferred over phenytoin and duration should be short, typically ≤7 days (NCS seizure guideline).
Examination-ready summary
Use INTERACT-2/ATACH-II to lower SBP carefully toward 140 mmHg, maintaining 130-150 mmHg and avoiding overshoot. Use INCH to reverse warfarin with 4F-PCC plus vitamin K. Use PATCH to avoid routine platelet transfusion. Use STICH/STICH-II to avoid routine craniotomy, but consider surgery for selected deteriorating or superficial lobar cases. Use MISTIE III and ENRICH to consider minimally invasive evacuation in selected patients, especially early lobar ICH in experienced centers. Use TICH-2 to avoid routine TXA. Use RESTART for individualized reintroduction of antiplatelet therapy.
Recent-evidence note: The newest comprehensive guideline is ESO-EANS 2025, PMID 40401775. A 2025 updated meta-analysis of intensive BP lowering is also available, PMID 40739079; it does not replace individualized BP decisions for large hematomas, SBP >220 mmHg, planned surgery, or renal vulnerability.
This is a shared conversation. Sign in to Orris to start your own chat.