Welcome to our Quarterly MISTIE III Safety Forum April 6, 2016

Size: px

Start display at page:

Download "Welcome to our Quarterly MISTIE III Safety Forum April 6, 2016"

Jessie McKinney
5 years ago
Views:

1 Welcome to our Quarterly MISTIE III Safety Forum April 6, 2016 Agenda: Update from our Surgical Centers: Where we stand surgically Issam Awad, MD, University of Chicago Vascular Defect Screening in MISTIE III Subjects Issam Awad, MD, University of Chicago Dialysis in the Setting of ICH Wendy Ziai, MD, MPH, Johns Hopkins University

2 Welcome to our Quarterly MISTIE III Safety Forum April 6, 2016 Agenda: Update from our Surgical Centers: Where we stand surgically Issam Awad, MD, University of Chicago Vascular Defect Screening in MISTIE III Subjects Issam Awad, MD, University of Chicago Dialysis in the Setting of ICH Wendy Ziai, MD, MPH, Johns Hopkins University

3 Surgical Center Report: Safety Forum April 6, 2016

4 Surgical Summary to Date (as of March 10, 2016) Patients Total 294 Surgical 144 (141 underwent surgery) Surgeon Status at time of surgery Pre-qualified 74 Qualified with probation 33 Fully qualified 34 Catheter Tract/ ICH/IVH Bleeds Symptomatic 4 * Asymptomatic 24 * * bleeds in surgical cases, only ICH/IVH expansion or CTH during active phase

5 Surgical Summary to Date Cont d Catheter Category Trajectory A Trajectory B Trajectory C Surgical cases that didn t go to surgery 144 SURGICAL CASES (141 underwent surgery) GOOD INITIAL 43 (66.2% of 65) 11 (35.5% of 31) 32 (71.1% of 45) *One case, the site exhausted their resources and did not attempt to retarget the clot. One case, site did not obtain permission from family for second procedure to retarget clot. 42 SUBOPTIMAL INITIAL 13 POOR INITIAL 32 CATHETERS REPOSITIONED AFTER DOSING OR REPLACED % Evacuated Absolute reduction (ml) % subjects reaching <15ml 19 (29.2% of 65) (16 dosed; 1 replaced and dosed; 1 replaced & reached endpoint) 3 (4.6% of 65) (2 replaced and dosed, 1 replaced and removed) 8 (1 replaced d/t dislodging by pt) 13 (41.9% of 31) (5 dosed; 4 replaced & dosed; 1 replaced & reached endpoint) 7 (22.6% of 31)* (6 replaced & dosed) 18 (includes 6 repositioned after dosing, 1 inadvertent pullback, and 1 replaced after dosing d/t dislodging) 10 (22.2% of 45) (10 dosed) 3 (6.7% of 45) (1 replaced & dosed, 1 replaced and removed) 6 (includes 1 new catheter placed during dosing to better target remaining clot) (1 pt herniated overnight before surgery, taken for crani; 1 pt improved overnight so surgeon didn t take to surgery, 1 prematurely randomized, ICH <30)

6 Surgical Summary to Date- Cont d Good Suboptimal Poor % Evacuated Absolute reduction (ml) % subjects reaching <15ml Prequalified (n=74) 44 (59.5% of 74) 20 (27.0% of 74) 10 (13.5% of 74) Qualified w/ probation (n=33) 18 (54.5% of 33) 14 (42.4% of 33) 1(3.0% of 33) Fully qualified (n=33) 23 (69.7% of 33) 9 (27.3% of 33) 1 (3.0% of 33) Note: 3 cases did not go to surgery so not counted here

7 6275 Command performance 1 st case at site (German site) 69 y/o female with HTN; site gave 3 doses Volume on stability CT 24.36ml Final volume 0.76ml

Lessons learned When asked for the secret to their success, site mentioned several things: Refresher meeting organized by BIOS Online training modules Multiple staff meetings with local MISTIE and

8 Lessons learned When asked for the secret to their success, site mentioned several things: Refresher meeting organized by BIOS Online training modules Multiple staff meetings with local MISTIE and hospital staff to present and explain the study PI additionally mentioned: Having the coordinator and surgeon be the same person makes it easier as there is less to coordinate during surgical enrollments Doing a demo case in the EDC to train herself on entering data and randomizing a patient helped make the process smoother

9 6277 Post randomization diagnosis of Moyamoya 56 y/o M with hx of noncompliant HTN Platelets 208, INR 1.1 at baseline CTA reported negative Patient randomized to medical arm

10 CTA report excerpt There is occlusion at M1 segment of right MCA with reconstitution of flow just distal to the occlusion, this may represent chronic occlusion versus less likely vasospasm. Overall the caliber of the distal anterior cerebral and middle cerebral arteries is small and irregular. It is not clear whether this is secondary to vasospasm and edema, or if it is related to contrast bolus timing.

12 2 weeks later, site did IR angiogram, definitively diagnosing the patient with Moyamoya

13 Lessons learned Site should consider possible etiology factors even when not spelled out by CTA. Basal occlusive disease should have suggested Moyamoya. SC and study leadership cannot weigh in if a study is uploaded as negative. We cannot divine that there was basal occlusive disease, nor independently read negative scans It is imperative that site PI views and clears all etiology scans

14 6265 asymptomatic (but significant) bleed post catheter removal 69 y/o male; hx of : CAD s/p CABG, MI, hyperlipidemia and A-Fib On Coumadin and ASA upon arrival INR 4.3 initially, pt received Vit K, FFP, PCC, corrected to 1.2 CTA and MRI negative Platelets dropped to 93 and developed chest pain, determined to be A-fib acting up, resolved with resumption of home med Isosorbide Bleed expanded during screening from 13.43ml on Dx CT to 73.48ml on final stability CT Patient randomized to surgery and received 8 total doses Patient not on any anticoags; Lovenox 30mg twice/day for DVT prophylaxis Day 3 through discharge

Stability CT Post initial placement Asymptomatic

doses - Catheter pulled back after 3 doses;

site wanted to pullback again; new bleeding noted

15 Stability CT Post initial placement Asymptomatic new bleed Post treatment during dosing, post 5 doses - Catheter pulled back after 3 doses; stabilized and continued dosing - After 5 doses, site wanted to pullback again; new bleeding noted on scan; appropriately stabilized before catheter was pulled back. Suggested further 1cm pullback, site agreed. Pulled back, appropriately stabilized, continued dosing

16 Asymptomatic new bleed 24 hours post catheter removal - INR stable at 1.2 throughout - GCS never below 12 (which was immediately post op). Throughout hospitalization, GCS Patient did have 4 hour episode of increased intensity of headache after dose 5

17 Site Evaluation of Hemorrhages Per site PI, the primary ICH expansion as well as the 2 remote small bleeds first noted on D5 appear to be hemorrhagic conversion of ischemic strokes. This is not surprising given the patient s extensive cardiac history. As noted in the EDC, pt has CAD s/p CABG, A-fib, cardiomyopathy, pulmonary HTN, hx cardiac arrest, hypertriglyceridemia, and HTN.

18 Initial MRI (Day 1) GRE: no hemorrhagic microangiopathy ADC: possible ischemic stroke

19 Final MRI (Day 11) GRE: hemorrhage in ischemic stroke ADC: expanded ischemic stroke with hemorrhagic conversion

20 Lessons Learned With initial bleeding expansion and subsequent bleeding during dosing, should we have resumed dosing? (protocol allowed but was this patient a bleeder?) Should the patient have been excluded because of ischemic stroke on initial MRI? Is this another example of a tendency of DVT prophylaxis to increase asymptomatic bleeding during treatment? Aspirin effect in a demonstrated bleeder?

21 Welcome to our Quarterly MISTIE III Safety Forum April 6, 2016 Agenda: Update from our Surgical Centers: Where we stand surgically Issam Awad, MD, University of Chicago Vascular Defect Screening in MISTIE III Subjects Issam Awad, MD, University of Chicago Dialysis in the Setting of ICH Wendy Ziai, MD, MPH, Johns Hopkins University

22 DIALYSIS IN THE SETTING OF ICH CIII and MIII

23 AKI FOLLOWING ICH Four studies, which included 615,623 subjects, examined the prevalence of AKI after ICH. Pooled prevalence rate of AKI after ICH was 19.0% (95% CI = 8.3% %). ICH patients are at risk for acute kidney injury (AKI) due to sepsis, liver failure and other infections and vasculitides

24 RRT IN ICH PATIENTS Specific parameters to guide renal replacement therapy (RRT) mode and timing in neurocritical care patients including ICH are lacking Indications for RRT that may be seen in acute ICH patients other than pre-existing need for dialysis include: severe metabolic acidosis volume overload uremia with end-organ damage refractory hyperkalemia overdose maintenance therapy for patients undergoing outpatient RRT

25 NEUROLOGIC COMPLICATIONS OF RRT RRT especially intermittent RRT (IRRT) has been reported to cause several severe neurologic complications: increased cerebral edema increased intracranial pressure new or worsening intracerebral or subdural hemorrhages new ischemic stroke mental status decline seizures Dialysis disequilibrium syndrome = well-known entity that encompass several symptoms such as headache, lethargy, confusion, seizures or brain herniation events related to increased cerebral edema with or without a known intracranial pathology

26 COHORT CIII (n=500) and MIII (n=300) subjects were reviewed for need for RRT 19 subjects underwent dialysis during the acute hospitalization CIII n=14 (3%) MIII n=5 (2%) Dialysis methods (per review of available source documentation) IHD (intermittent hemodialysis): 8 CRRT (continuous renal replacement therapy) encompasses: CVVHD: continuous veno-veno hemodialysis: 8 CAVHD: continuous arterio-venous hemodialysis: 0 SLED: sustained low-efficiency dialysis: 0 PD: peritoneal dialysis: 0 UTD (unable to determine): 3

27 TIMELINE Dialysis therapy was initiated a mean of 10.9 days post symptom onset for 17 subjects (range: 1-26 days) 2 subjects continued pre-randomization dialysis For those subjects (n=11) who died, mean time to death after start of dialysis was 62.4 days (range: days)

28 DIALYSIS AND DEATH CIII Dead Yes Dead No Total p Dialysis Yes Dialysis No Total MIII Dead Yes Dead No Total p Dialysis Yes Dialysis No Total Three subjects died within 48 hours of dialysis start One received CVVHD (CIII) Two received HD (MIII) CIII & MIII Dead Yes Dead No Total p Dialysis Yes Dialysis No Total

29 Stability: Prior to randomization Day 2: Hours post dialysis Day 3: Day of death

30 CIII Dead Yes Dead No Total p Renal insufficiency prior to rnd Yes Renal insufficiency prior to rnd No Total RENAL INSUFFICIENCY ONSET PRIOR TO RANDOMIZATION AND DEATH MIII Dead Yes Dead No Total p Renal insufficiency prior to rnd Yes Renal insufficiency prior to rnd No Total CIII & MIII Dead Yes Dead No Total p Renal insufficiency prior to rnd Yes Renal insufficiency prior to rnd No Total

31 CIII Dead Yes Dead No Total p Renal insufficiency post rnd Yes Renal insufficiency post rnd No Total MIII Dead Yes Dead No Total p Renal insufficiency post rnd Yes Renal insufficiency post rnd No Total CIII & MIII Dead Yes Dead No Total p Renal insufficiency post rnd Yes Renal insufficiency post rnd No Total RENAL INSUFFICIENCY ONSET POST RANDOMIZATION AND DEATH

32 HYPOTENSION ONSET POST RANDOMIZATION AND DEATH CIII Dead Yes Dead No Total p Hypotension post rnd Yes Hypotension post rnd No Total MIII Dead Yes Dead No Total p Hypotension post rnd Yes Hypotension post rnd No Total Two subjects on dialysis experienced hypotension: one during dialysis one 8 days prior to dialysis CIII & MIII Dead Yes Dead No Total p Hypotension post rnd Yes Hypotension post rnd No Total

33 CHOICE OF TYPE OF RRT IN ACUTE ICH CRRT is chosen for following indications: hemodynamically unstable a higher mean arterial blood pressure is required to enhance cerebral perfusion severe cerebral edema poor intracranial compliance and high intracranial pressure rapid fluid and solute concentration shifts may not be tolerable Therefore, in the acute phase of a neurologic injury such as ICH where maintaining CPP is important, IHD should not usually be the first modality chosen Recommendation: communicate with your renal consultants and if RRT is necessary during acute phase of ICH, 1 st choice is CVVHD until cerebral edema has started to resolve and risk of herniation is low

34 CONSIDERATIONS DURING THE SCREENING ASSESSMENT Does the patient have acute or chronic renal failure? What is the severity of the patient s chronic renal failure and what are the requirements (or not) for dialysis? What is the likelihood of 1 year survival (exclusion factor: Not expected to survive to the day 365 visit due to comorbidities ), in evaluating the patient's candidacy for MISTIE III?

Welcome to our MISTIE III Safety Forum September 12, 2016

Welcome to our MISTIE III Safety Forum September 12, 2016 Agenda: Update from our Surgical Centers: Where we stand surgically Mario Zuccarello, MD, University of Cincinnati Revisiting the Importance of