Synergistic Minimally Invasive Surgery Plus Alteplase and Deferoxamine in ICH

Not Applicable

Not yet recruiting

• Conditions: Intracerebral Hemorrhage; ICH - Intracerebral Hemorrhage
• Interventions: Drug: Alteplase; Other: Standard Medical Care (SMD); Drug: Deferoxamine

• Registration Number: NCT07162363
• Lead Sponsor: University of Illinois at Chicago

Brief Summary

This is a single-center, randomized, open-label pilot trial designed to evaluate the safety, feasibility, and preliminary efficacy of combining minimally invasive surgery (MIS) plus intralesional alteplase and intravenous deferoxamine (DFX) for the treatment of spontaneous intracerebral hemorrhage (ICH), compared with MIS plus alteplase or standard medical care. A total of 63 patients (21 per arm) will be enrolled and followed for 90 days.

Patients in the investigational arm will undergo MIS with intralesional alteplase administration, combined with intravenous DFX at 32 mg/kg/day for 3 consecutive days. The MIS procedure will include clot aspiration and intralesional alteplase administration every 8 hours for up to nine doses. Patients in the standard medical care arm will be treated according to American Heart Association (AHA) and European Stroke Organization (ESO) guidelines for acute ICH management.

This pilot trial will be the first to test a dual-modality approach-clot evacuation and dissolution combined with biochemical neuroprotection in ICH patients. The results will provide feasibility and safety data, generate preliminary efficacy signals, and guide the design of a future multicenter efficacy trial.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-19
• Study First Submitted QC: 2025-09-04
• Last Update Submitted: 2025-09-04
• Study First Posted: 2025-09-09
• Last Update Posted: 2025-09-09
• Study Start: 2025-11-15
• Primary Completion: 2026-12-30
• Study Completion: 2026-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

Participants must meet all the following criteria:

1. Age ≥ 18 and ≤ 80 years

2. Spontaneous supratentorial ICH confirmed by CT or CTA, with hematoma volume:

   • ≥30 mL on initial diagnostic CT, OR
   • ≥25 mL on stability CT performed ≥6 hours after diagnostic CT, Clot growth must be less than 5 mL between scans to be eligible A second stability scan at least 12 hours later is allowed if clot expanded >5 mL

3. NIHSS score ≥ 6 at enrollment

4. GCS > 6 and ≤14 on admission

5. Symptoms onset ≤ 24-48 hours before diagnostic CT

   • Use "last known well" for wake-up strokes
   • Unknown onset is exclusionary

6. SBP < 180 mm Hg sustained for at least 6 hours prior to randomization

7. Randomization must occur between 12 and 72 hours from initial diagnostic CT done at UIC or in case of transfers, at other institutions.

8. Functionally independent pre-ICH, defined as mRS 0-1

9. Written informed consent obtained from patient or legal representative

Exclusion Criteria

1. Infratentorial hemorrhage (e.g., brainstem or cerebellar hematoma).

2. Hemorrhage due to secondary causes: trauma, AVM, aneurysm, Moyamoya disease, hemorrhagic conversion of ischemic stroke, tumor, or vascular anomaly (diagnosed on imaging).

3. Recurrent ICH within the past year.

4. Intraventricular hemorrhage (IVH) requiring surgical treatment for trapped ventricle or mass effects (e.g., endoscopic evacuation). EVD is permitted.

5. Evidence of irreversible impaired brainstem function (e.g., bilateral fixed dilated pupils, decerebrate posturing).

6. GCS ≤ 5 or NIHSS item 1A score = 3.

7. Thalamic ICH with midbrain extension and third nerve palsy.

8. Clinical indication for emergent surgical hematoma evacuation, as determined by treating neurosurgeons.

9. NIHSS score < 6 (too mild to benefit).

10. Expected withdrawal of care, implementation of a new DNR/CMO order within the first 72 hours, or life expectancy < 90 days due to comorbid conditions.

11. Creatinine ≥ 2.0 mg/dL or evidence of severe renal impairment.

12. Active hepatic failure or severe hepatic disease.

13. Pregnancy, positive pregnancy test, or breastfeeding.

14. Severe iron deficiency anemia (Hgb < 7 g/dL, ferritin < 15 ng/mL, or requiring blood transfusions).

15. Active systemic infection (e.g., sepsis, subacute bacterial endocarditis) or patients with confirmed aspiration, pneumonia, or bilateral pulmonary infiltrates on chest imaging prior to enrollment.

16. Active internal bleeding (GI, GU, retroperitoneal, pulmonary).

17. History of mechanical heart valve (bioprosthetic valves allowed).

18. Known left atrial/ventricular thrombus or high embolic risk (e.g., mitral stenosis + AFib).

19. Any coagulopathy:

    Platelet count <100,000 INR > 1.3-1.4 or not correctable within 6 hours Use of direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitors (e.g., rivaroxaban, apixaban), or LMWH at presentation Long-term anticoagulation that cannot be safely stopped (e.g., mechanical valve needing Coumadin)

20. Allergy or known hypersensitivity to DFX or rtPA.

21. Active alcohol or drug use, or a drug screen positive for cocaine, that impairs adherence to follow-up.

22. Patients known or suspected of being unable to comply with the study protocol (e.g., alcoholism, drug dependency, noncompliance, living in another state).

23. Significant respiratory disease (e.g., COPD, pulmonary fibrosis, chronic home O₂ use) or FiO₂ >0.35 (>4 L/min) prior to enrollment.

24. Sepsis, systemic inflammatory response syndrome (SIRS), or shock at presentation (e.g., temp >100.4°F or <96.8°F; HR >90; RR >20 or PaCO₂ <32 mmHg; WBC >12, <4, or bands >10%; SBP <90 mmHg).

25. Presence of ≥4 risk modifiers for ARDS prior to enrollment:

    Tachypnea (RR >30) SpO₂ < 95% Obesity (BMI >30) Acidosis (pH < 7.35) Hypoalbuminemia (albumin < 3.5 g/dL) Concurrent chemotherapy

26. Known severe hearing loss.

27. Taking iron supplements containing ≥325 mg ferrous iron or prochlorperazine

28. Patients with heart failure taking >500 mg vitamin C daily

29. Any condition that, in the judgment of the investigator, might increase risk to the patient or interfere with outcome assessments.

30. Concurrent participation in another interventional research protocol (observational studies allowed).

    Special Populations

31. Adults who are unable to provide informed consent may be enrolled if a legally authorized representative provides consent on their behalf.

32. Individuals under 18 years: excluded.

33. Prisoners: excluded.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MIS plus Alteplase AND IV Deferoxamine	Alteplase	Participants will undergo minimally invasive surgery (MIS) for hematoma evacuation, with alteplase administered via catheter directly into the site of ICH to promote clot dissolution, and intravenous deferoxamine (DFX) given to reduce iron-mediated neurotoxicity.
MIS plus Alteplase AND IV Deferoxamine	Deferoxamine	Participants will undergo minimally invasive surgery (MIS) for hematoma evacuation, with alteplase administered via catheter directly into the site of ICH to promote clot dissolution, and intravenous deferoxamine (DFX) given to reduce iron-mediated neurotoxicity.
MIS plus Alteplase	Alteplase	Participants will undergo minimally invasive surgery (MIS) for hematoma evacuation, with alteplase administered via catheter directly into the site of ICH to promote clot dissolution.
Standard Medical Care (SMC)	Standard Medical Care (SMD)	Participants receive standard medical management for ICH without MIS or deferoxamine, serving as the control group.

Primary Outcome Measures

Name	Time	Method
Safety and Feasibility: Treatment-Related Adverse Events Assessed by CTCAE v4.0 and Completion of Study Procedures	Post-treatment day 90	Safety will be assessed by recording all treatment-related adverse events (AEs) and serious adverse events (SAEs) occurring within 90 days post-treatment, graded according to CTCAE v5.0. Feasibility will be evaluated by the successful completion of study procedures, including minimally invasive surgery plus intracerebral alteplase administration via catheter and intravenous deferoxamine infusion.
Modified Rankin Scale	Post-treatment day 30, day 90	Functional outcome will be assessed using the Modified Rankin Scale (mRS), which ranges from 0 to 6, where 0 indicates no symptoms and 6 indicates death. Higher scores correspond to worse functional outcomes.

Secondary Outcome Measures

Name	Time	Method
Mortality	Post-treatment day 90
Hematoma and perihematomal edema volume	Post-treatment day 30, day 90	Hematoma and perihematomal edema volumes will be measured on serial imaging studies (CT or MRI).
Iron, inflammatory, and fibrinolytic marker concentrations in plasma	From Baseline through 90 days post-treatment	Blood samples (5-10 ml) will be collected to evaluate systemic biochemical responses in arm 1. Samples will be analyzed for iron, inflammatory mediators, and fibrinolytic activity at these time points.; Exploratory: \~6 hours after DFX initiation on Day 1 (subset) B0: Baseline (Pretreatment: prior to DFX and alteplase administration) B1: 24 hours after DFX initiation (±3 h) B2: 48 hours after DFX initiation (±3 h) B3: 72 hours after DFX initiation (±3 h) B4: 30-day follow-up B5: 60-day follow-up B6: 90-day follow-up
Iron, inflammatory, and fibrinolytic marker concentrations in surgical cavity fluid	Immediately after catheter placement through 72 hours post-first alteplase dose (T0-T4)	Small-volume (1-2 ml) surgical cavity fluid samples will be collected via the indwelling catheter in arm 1 and arm 2 patients. Samples will be analyzed for iron concentration, inflammatory mediators, and fibrinolytic activity at the following time points: T0: Immediately after catheter placement, before first alteplase dose T1: End of 1-hour clamp after first alteplase dose T2: 24 hours after first alteplase dose (±3 h) T3: 48 hours after first alteplase dose (±3 h) T4: 72 hours after first alteplase dose or at catheter removal, whichever comes first
Intensive Care Unit (ICU) and Hospital Length of Stay	Within 3 months after randomization	Total length of initial ICU and hospital stay within 3 months after randomization

Trial Locations

Locations (1)

University of Illinois Hospital & Health Sciences System (UI Health); 🇺🇸 Chicago, Illinois, United States