Title: INTERACT3 Trial – A Landmark in Acute Intracerebral Hemorrhage Management Description: Intracerebral hemorrhage (ICH) remains one of the most devastating forms of stroke, with high rates of morbidity and mortality, and limited evidence-based acute interventions. The INTERACT3 trial (Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial), published in The Lancet in 2023, represents a pivotal moment in the management of ICH, especially in low- and middle-income countries. This SlideShare presentation provides a comprehensive breakdown of the INTERACT3 trial, its design, interventions, findings, and how it changes real-world emergency and neurocritical care for patients presenting with acute ICH. ⸻ 🔹 What is INTERACT3? INTERACT3 was the first-ever phase 3, pragmatic, international, cluster-randomized controlled trial designed to evaluate the benefit of a multimodal, protocol-based care bundle in improving functional outcomes in patients with acute spontaneous ICH. ⸻ 🔹 Study Design & Setting • Published in The Lancet, 2023 • Included 94 hospitals across 10 countries (mostly LMICs, including India and China) • Enrolled over 7200 patients with acute ICH presenting within 6 hours of symptom onset • Used cluster randomization for real-world applicability and health system integration ⸻ 🔹 The Care Bundle Interventions The INTERACT3 protocol emphasized early, goal-directed management of 4 key physiological parameters within the first 6 hours: 1. Blood Pressure Control: Target SBP <140 mmHg using IV antihypertensives 2. Glycemic Management: Maintain blood glucose <180 mg/dL 3. Temperature Control: Avoid fever; antipyretics if temp >37.5°C 4. Reversal of Anticoagulation (when applicable): Prompt reversal of warfarin or DOAC effect All interventions were implemented as part of a standardized treatment protocol, facilitated by checklists, training, and hospital-level support. ⸻ 🔹 Key Results • Improved functional outcomes at 6 months (measured by modified Rankin Scale) in the intervention group • Significant reduction in death or major disability • No increase in adverse events, rebleeding, or infections • Demonstrated that organized, early critical care improves prognosis even without advanced neurosurgical interventions ⸻ 🔹 Clinical Impact INTERACT3 is practice-changing, especially in resource-limited settings. It shows that: • A protocol-driven approach to BP, glucose, temperature, and anticoagulation reversal is safe, feasible, and effective • Emergency departments and stroke teams can implement these low-cost measures quickly to improve outcomes • It raises the standard of care for ICH in primary and secondary hospitals, not just tertiary centers ⸻ 🔹 Who Should View This? This presentation is ideal for: • Emergency physicians • Neurologists & stroke teams • ICU staff • General physicians managing acute ICH • Hospital administrators and protocol developers • Medical stud

1. Dr. Shanif Muhammed

2. Spontaneous ICH

3. Acute Management of Spontaneous ICH

4. 2022 AHA/ASA Spontaneous ICH Guideline Recommendations

5. Early Intensive BP Lowering

6. Bundled Care in ICH

8. 2022 AHA/ASA Spontaneous ICH Guideline
• "The potential synergistic benefits of a bundle of care, including BP
lowering and reversal of anticoagulation, should be studied, as well as
specific care pathways"
• Does bundled care improve functional outcomes?
Bundled Care in ICH

9. The third intensive care bundle with blood
pressure reduction in acute cerebral
hemorrhage trial (INTERACT3)

10. Study Rationale
1st randomized controlled trial to evaluate a
care bundle that included blood pressure
lowering in acute ICH
BP Management Blood Glucose
Control
Treatment of
Pyrexia
Anticoagulation
Reversal

11. Study Design
Pragmatic, international, multicenter, blinded endpoint, stepped wedge,
cluster randomized controlled trial

12. • Age 18 years
≥
• Spontaneous ICH confirmed by clinical history and CT scan
• Presentation within 6 hours of stroke onset
INCLUSION CRITERIA
• ICH secondary to structural abnormality in the brain or reperfusion
therapy
• Low likelihood of adherence to study treatment and/or follow-up regimen
EXCLUSION CRITERIA

13. Intervention
BP Management
Blood Glucose
Control
Treatment of
Pyrexia
Anticoagulation
Reversal
Early, intensive BP
management
• Goal SBP < 140
mmHg within 1
hour
• Threshold of SBP
130 mmg for
treatment
cessation
• Using fresh
frozen plasma
(FFP) or PCC
• Goal INR < 1.5
within
1 hour
• Goal 110-140
mg/dL for patients
without diabetes
• Goal 140-180
mg/dL for patients
with diabetes
• As soon as
possible after
treatment
initiation
• Goal < 37.5°C
within
1 hour

14. Outcomes
The primary outcome was functional recovery at 6 months based on the
modified Rankin scale, defining scores of 0 and 1 as favourable.
Secondary outcomes:
• Dichotomous analysis of mRS scores at 6 months
• Death at 6 months
• Death or neurologic deterioration at 7 days
• Health-related quality of life
• Residence at home at 6 months
• Hospital discharge by day 7

15. Statistical analysis
90% power to detect a common odds ratio (OR) of 0.8 for worse functional
outcome at 6 months
• Target sample size of 8360 patients from 110 sites
• a= 0.05
• Intraclass correlation coefficient of 0.04

16. Baseline characteristics

17. Care bundle implementation

19. Medications in 1st 24 hrs

20. Outcomes
Using an ordinal analysis, the patients in the intervention group had better functional outcomes
on the modified Rankin score (OR 0.86, 95% CI 0.76-0.97, p=0.015).
The bundled care groups also had a lower odds of death (OR 0.77, 95% CI 0.63-0.95), although
that difference was not statistically significant after their planned adjustments.
There was no statistical difference in the more standard dichotomous outcomes, using a mRs 0-
2 as the good outcome (OR 0.89, 95%CI 0.78-1.02).

21. Reduced mortality at 6 months
• Unadjusted OR 0.77; 95% CI 0.63-0.95; p= 0.015
• Adjusted OR 0.84; 95% CI 0.65-1.07; p= 0.16
No difference in major disability (mRS score 3-5) at 6 months
• OR 0.96;95% C| 0.83-1.11; p= 0.56
No difference in death or neurologic deterioration at 7 days
• OR 0.89; 95% CI 0.77-1.03; p= 0.12
Fewer serious adverse events
• 516/3221 (16%) vs. 767/3815 (20.1%); p= 0.0098

22. Author’s conclusions
Findings support the adoption of an active protocol for intensive blood
pressure lowering and the associated management of key abnormal
physiological variables to improve the recovery of patients presenting with
acute ICH
1st phase 3 multicenter randomized controlled trial to show a positive
outcome for an acute treatment of ICH

23. Strengths