MISTIE-3 and MISTIE-III

Clinical Trial Details

Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III (MISTIE-III)

A phase III, randomized, case-controlled, open-label, 500-subject clinical trial of minimally invasive surgery plus rt-PA in the treatment of intracerebral hemorrhage (ICH).

Key Findings

MISTIE 3: At 1-year post-ICH, functional recovery was not improved when comparing the image-guided minimally invasive MISTIE procedure + alteplase to traditional medical therapy to treat medium to large intracerebral hemorrhage. It may reduce death, and more benefit was seen with a smaller residual volume.

MISTIE III: The more the volume of the ICH is reduced during surgery to treat intracerebral hemorrhage, the greater the likelihood of a good functional outcome, with ≤15 mL indicated as a threshold.

Detailed Results

MISTIE 3: Neutral results - At 1-year post-ICH, functional recovery was not improved when comparing the image-guided minimally invasive MISTIE procedure + alteplase for 3 days to traditional medical therapy: 45% had mRS 0-3 in MISTIE patients vs 41% in medical treatment group (p=0.33). More benefit was seen with smaller residual volumes. MISTIE procedure vs medical therapy was safe at 30 days.

MISTIE lll: The more the volume of the ICH is reduced during surgery, the greater the likelihood of a good functional outcome, with a threshold of ≤15 mL. More surgeon experience was associated with lower residual volume results.

  • mRS 0-3 vs 4-6 at 365 days: adjusted difference 3%, p=0.47 - primary endpoint
  • 59% of surgical patients had <15 mL EOT volume – surgical goal
  • eGOS score (degree of disability): MISTIE (38%) vs medical (34%)
  • Safety at 30-days - Death: MISTIE 9% vs medical treatment 15%, p=0.07. Bleeding: MISTIE 2% vs medical treatment 0%. Brain infection: MISTIE 1% vs medical treatment 0%, p=0.16. Serious adverse event ≥ 1: MISTIE 30% vs medical treatment 33%.
  • ICH removal and good outcome: p>0.001
  • <15 mL residual hematoma volume: mRS (10%), eGOS (12%); p=0.01
  • ICH removal of <15 mL = benefit: adjusted odds ratio (AOR)=1.75, p=0.030
  • mRS 0-3 corelated with efficiency of clot removal: AOR=0.63/10 mL time-averaged ICH, p<0.001
  • Better ICH evacuation was associated with deep ICH (OR 2.08, p=0.03) and greater site and surgeon experience (P<0.0001)

MISTIE-3 With Dan Hanley, MD and Issam Awad, MD

Bruce Ovbiagele, MD, MSc, MAS, MBA interviews Dan Hanley, MD and Issam Awad, MD, co-prinicipal investigators of the MISTIE 3 trial about what the results suggest for treating patients with ICH.

MISTIE 3

Purpose: to compare 1-year functional recovery with minimally invasive surgery using the MISTIE procedure, a catheter-based ICH clot removal approach for stable large hematomas, to standard therapy.

Trial Design: Phase 3; n=499; 74 sites; Randomized to MISTIE + alteplase for 3 days, or standard medical therapy. 61% male; average age 61.

Primary Endpoints: blinded assessment of modified Rankin Scale (mRS) at 1 year.

MISTIE 3 Results
At 365 DaysMISTIEeGOSStandard
Medical
Treatment
P Value
Clot volume reduced
to ≤ 15 mL benefit
10%12% 0.01
Death9%15%0.07
Rebleed2%0% 
Brain infection1%0%0.16
mRS @365 days
adjusted 3%
difference
0-34-60.47
Good recovery45%41% 
eGOS score (degree of
disability) 4% difference
38%34% 

Results: Neutral results - At 1-year post-ICH, functional recovery was not improved when comparing the image-guided minimally invasive MISTIE procedure + alteplase for 3 days to traditional therapy. Mortality was not increased, and more benefit was seen with smaller residual volumes. Compared to medical therapy, the MISTIE procedure was safe.

MISTIE III

Purpose: Examination of the amount of blood removal during surgery for large intracerebral hemorrhages (ICH) and better functional outcomes at one year.

Trial Design: a surgical intervention cohort of the MISTIE lll trial; n=242; measured surgical performance for the efficacy and degree of clot removal and functional outcomes (mRS 0-3) at 1 year.

Primary Endpoints: benefits (functional recovery) if surgical goal of <15 mL at end of treatment is achieved. Modified Rankin Scale (mRS) 0-3 or ≥70% volume reduction at 1 year.

MISTIE III
 End-of-therapy
goal <15 mL
End-of-therapy
goal <15 mL
Increasing end-of-
therapy size
mRS 0-3AOR 1.75,
p=0.030
AOR 0.76,
p=0.238
Decrease in AOR
(1.80-1.53) P=0.068
mRS 0-3 correlated with amount of clot removal
AOR=0.63/10 mLtime-averaged ICH, p<0.001
Deep ICH had better blood removal
OR 2.08, p=0.03
Deep ICH had better blood removal found with more experience
for sites and surgeons. p<0.0001

Results: The more the volume of the ICH is reduced during surgery, the greater the likelihood of a good functional outcome, with ≤15 mL indicated as a threshold. 59% of surgical patients had <15 mL EOT volume. More surgeon experience was associated with lower residual volume results.

Background

MISTIE 3: Assessment of functional outcome using minimally invasive thrombectomy (image-guided catheter evacuation and thrombolysis) to achieve a residual volume of 15 ml in intracerebral hemorrhage (ICH).
MISTIE lll: evaluation of amount of blood removed during surgery for ICH and functional outcome.

Trial design: phase 3, open-label, image-guided randomization, blinded, case-controlled trial. N=499; surgical cohort 242 patients; 78 sites; Patients randomized to MISTIE + 1.0 mg alteplase q8h up to 9 doses, or standard medical therapy.

Patients: 61% male; average age 61.

Primary endpoints: good functional outcome measured by modified Rankin Scale (mRS) in intention to treat. (mRS measures degree of disability or dependence in daily activities.)

  • MISTIE 3 – modified Rankin Scale (mRS) score 0-3 vs. 4-6 at 1 year after ICH = good functional outcome
  • MISTIE lll – surgical: functional recovery (modified Rankin Scale (mRS) 0-3 at 1 year after ICH) if ICH blood volume at the end of surgery of <15 mL or ≥70% volume reduction is achieved.

Other Endpoints: MISTIE lll – surgical outcomes

  • 30-day serious adverse events:  all-cause mortality, brain bleeding, brain infection
Primary endpoints: (mRS = ICH (functional recovery - degree of disability or dependence in the daily activities)
  • MISTIE 3: modified Rankin Scale (mRS) score 0-3 vs. 4-6 at 1 year after
  • MISTIE III: benefits (functional recovery) if surgical goal of <15 mL at end of treatment is achieved. Modified Rankin Scale (mRS) 0-3 or ≥70% volume reduction at 1 year after ICH.
Secondary endpoints: MISTIE III
  • Extended Glasgow Outcome Scale (eGOS) score upper good recovery (UGR) through upper severe disability (US) vs. lower severe disability (LS) through death at 365 days after ICH.
  • All-cause mortality longitudinally from ICH to 365 days
  • Clot removal (amount of residual blood)
  • Patient disposition
Other endpoints: MISTIE III
  • 30-day mortality and safety: all-cause mortality, brain bleeding, infection, SAE’s

References

Related Science

Key Words
Intracerebral hemorrhage, ICH, brain hemorrhage, minimally invasive surgery, rt-PA

Related Clinical Topics
Stroke, intracerebral hemorrhage, rehabilitation, functional outcome, intracerebral hemorrhage, modified Rankin Scale, tissue plasminogen activator

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