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).

Study Overview

• Status: Completed
• Conditions: Intracerebral Hemorrhage
• Intervention / Treatment: Drug: rt-PA

Detailed Description

Primary Objectives:

Efficacy: Demonstrate that minimally invasive surgery (MIS) plus recombinant tissue plasminogen activator (rt-PA) for three days improves functional outcome by a 12% increase in the modified Rankin Scale (mRS) score 0-3 compared to medically treated subjects assessed at 365 days.

Secondary Objective:

Demonstrate that the end of treatment volume and percent of ICH reduction from MIS+rt-PA is related to improved functional outcome, as compared to medically treated subjects.

Safety:

Demonstrate that early use of MIS+rt-PA for three days is safe for the treatment of ICH relative to rates of mortality, rebleeding, and infection in the medically treated subject at 30 days.

• Study Type: Interventional
• Enrollment (Actual): 499
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2015
      • Royal Prince Alfred Hospital
  • South Australia
    • North Adelaide, South Australia, Australia, 5006
      • Royal Adelaide Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • McMaster University
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute, McGill University
• China
  • Beijing, China, 100700
    • Bayi Brain Hospital, Beijing Military General Hospital
  • Chongqing, China, 400038
    • Southwest Hospital, Third Military Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510180
      • Guangzhou First People's Hospital
• Germany
  • Bonn, Germany, 53127
    • University of Bonn
  • Heidelberg, Germany, 69120
    • University of Heidelberg
  • Mainz, Germany, D-55131
    • University of Mainz
  • Munich, Germany, 81925
    • University of Munich
• Hungary
  • Debrecen, Hungary, 4032
    • University of Debrecen
  • Szeged, Hungary, 6720
    • University of Szeged
  • Baranya County
    • Pecs, Baranya County, Hungary, 7623
      • University of Pécs
• Israel
  • Petach Tikva, Israel
    • Rabin Medical Center
  • Ramat-Gan
    • Tel Hashomer, Ramat-Gan, Israel, 52621
      • The Chaim Sheba Medical Center at Tel HaShomer
• Spain
  • Barcelona, Spain, 08041
    • Hospital De La Santa Creu I Sant Pau
  • Barcelona, Spain, 08035
    • Vall d'Hebron University Hospital
  • Barcelona, Spain, 08907
    • Bellvitge
  • Barcelona, Spain
    • Hospital Universitario Mutua de Terrassa
  • Valladolid, Spain, 47012
    • Hospital Universitario Rio Hortega
  • Biscay
    • Barakaldo, Biscay, Spain, 48903
      • Hospital Universitario Cruces
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • South Glasgow University Hospital
  • Newcastle upon Tyne, United Kingdom
    • Newcastle Royal Victoria Infirmary
  • Southampton, United Kingdom, SO16 6YD
    • University of Southampton Hospital
  • Manchester
    • Salford, Manchester, United Kingdom, M6 8HD
      • Salford Royal NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
    • Phoenix, Arizona, United States, 85006
      • Banner Good Samaritan Hospital
  • California
    • Carmichael, California, United States, 95608
      • Mercy San Juan Medical Center
    • La Jolla, California, United States, 92037
      • Scripps Health
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • San Diego, California, United States, 92103
      • University of California, San Diego
    • Stanford, California, United States, 94305
      • Stanford University
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic, Jacksonville
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Gwinnett Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60612
      • Rush University
    • Evanston, Illinois, United States, 60201
      • Northshore University Health System, Evanston
    • Maywood, Illinois, United States, 60305
      • Loyola University Chicago
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Michigan
    • Ann Arbor, Michigan, United States, 48190
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Heath System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Hospital of Kansas City
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers - Robert Wood Johnson Medical School
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • New York
    • Bronx, New York, United States, 10467
      • Albert Einstein College of Medicine - Montefiore Medical Center
    • Buffalo, New York, United States, 14203
      • University of Buffalo
    • Manhasset, New York, United States, 11030
      • North Shore Long Island Jewish Health System
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • Syracuse, New York, United States, 13210
      • State University of New York, Upstate Medical University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence Brain and Spine Institute
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University School of Medicine
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern at Dallas
    • Houston, Texas, United States, 77030
      • University of Texas, Houston
    • San Antonio, Texas, United States, 78229
      • University of Texas at San Antonio
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Neurosciences Institute
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Medical Center
    • Falls Church, Virginia, United States, 22042
      • Fairfax INOVA Hospital
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Spontaneous supratentorial ICH ≥ 30 mL diagnosed using radiographic imaging (computerized tomography (CT), computerized tomography angiography (CTA), etc.), with a Glasgow Coma Scale (GCS) ≤ 14 or a NIHSS ≥ 6.
• Stability CT scan done at least 6 hours after diagnostic CT showing clot stability (growth < 5 mL as measured by ABC/2 method).
• Symptoms less than 24 hours prior to diagnostic CT (dCT) scan (an unknown time of onset is exclusionary).
• Ability to randomize between 12 and 72 hours after dCT.
• Systolic Blood Pressure (SBP) < 180 mmHg sustained for six hours recorded closest to the time of randomization.
• Historical Rankin score of 0 or 1.
• Age ≥ 18 and older.

Exclusion Criteria:

• Infratentorial hemorrhage.
• Intraventricular hemorrhage (IVH) requiring treatment for IVH-related (casting) mass effect or shift due to trapped ventricle. External ventricular drain (EVD) to treat intracranial pressure (ICP) is allowed.
• Thalamic bleeds with apparent midbrain extension with third nerve palsy or dilated and non-reactive pupils. Other (supranuclear) gaze abnormalities are not exclusions. Note: Patients with a posterior fossa ICH or cerebellar hematomas are ineligible.
• Irreversible impaired brain stem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS ≤ 4.
• Ruptured aneurysm, arteriovenous malformation (AVM), vascular anomaly, Moyamoya disease, hemorrhagic conversion of an ischemic infarct, recurrence of a recent (< 1 year) hemorrhage diagnosed with radiographic imaging.
• Patients with unstable mass or evolving intracranial compartment syndrome.
• Platelet count < 100,000; international normalized ratio (INR) > 1.4.
• Any irreversible coagulopathy or known clotting disorder.
• Inability to sustain INR ≤ 1.4 using short- and long-active procoagulants (such as but not limited to NovoSeven, Fresh Frozen Plasma (FFP), and/or vitamin K).
• Subjects requiring long-term anti-coagulation are excluded. Reversal of anti-coagulation is permitted for medically stable patients who can realistically tolerate the short term risk of reversal. Patient must not require Coumadin (anticoagulation) during the first 30 days, and normalized coagulation parameters must be demonstrated, monitored closely and maintained during the period of brain instrumentation.
• Use of Dabigatran, Apixaban, and/or Rivaroxaban (or a similar medication from the similar medication class) prior to symptom onset.
• Internal bleeding, involving retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts.
• Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures, etc.) or site of recent surgical intervention.
• Positive urine or serum pregnancy test in pre-menopausal female subjects without a documented history of surgical sterilization.
• Allergy/sensitivity to rt-PA.
• Prior enrollment in the study.
• Participation in a concurrent interventional medical investigation or clinical trial. Patients in observational, natural history, and/or epidemiological studies not involving an intervention are eligible.
• Not expected to survive to the day 365 visit due to co-morbidities and/or are do not resuscitate (DNR)/ do not intubate (DNI) status prior to randomization.
• Any concurrent serious illness that would interfere with the safety assessments including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, and hematologic disease.
• Patients with a mechanical heart valve. Presence of bio-prosthetic valve(s) is permitted.
• Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, or subacute bacterial endocarditis.
• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• In the investigator's opinion, the patient is unstable and would benefit from a specific intervention rather than supportive care plus or minus MIS+rt-PA removal of the ICH.
• Inability or unwillingness of subject or legal guardian/representative to give written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MIS plus rt-PA management; Subjects randomized to the Minimally Invasive Surgery (MIS) plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.	Drug: rt-PA; Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.; Other Names: Alteplase; Activase; CathFlo
No Intervention: Medical management; Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dichotomized, Adjudicated Modified Rankin Scale Score 0-3 vs. 4-6 at 365 Days Post Ictus (Adjusted)	Dichotomized, adjudicated, cross-sectional modified Rankin Scale (mRS) score 0-3 vs. 4-6 at 365 days post-ictus, adjusting for baseline (pre-randomization) variables used in covariate adaptive randomization as well as the clinically established severity variables IVH size and ICH location (lobar or deep). Ictus refers to symptom onset. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from: 0=No symptoms at all, 1=No significant disability, 2=Slight disability, 3=Moderate disability, 4=Moderately severe disability, 5=Severe disability and 6=death. Dichotomized scores are: 0-3=No symptoms to moderate disability requiring some assistance; 4-6=Moderately severe disability requiring complete assistance to death.	Day 365

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dichotomized Extended Glasgow Outcome Scale (eGOS) Score UGR-US vs. LS-Death at 365 Days Post Ictus (Adjusted)	Dichotomized, cross-sectional 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 post ictus, adjusting for baseline (pre-randomization) variables used in covariate adaptive randomization as well as the clinically established severity variables IVH size and ICH location (lobar or deep). The eGOS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored as: 1=Death, 2=Vegetative state, 3=Lower severe disability, 4=Upper severe disability, 5=Lower moderate disability, 6=Upper moderate disability, 7=Lower good recovery, 8=Upper good recovery. Dichotomous variable coding is as follows: 1=codes 4-8, 0=codes 1-3.	Day 365
All Cause Mortality Longitudinally From Ictus to 365 Days (Adjusted)	By group comparison of mortality from ictus to 365 days adjusted for baseline severity.	Day 365
Clot Removal (Amount of Residual Blood)	Relationship between clot removal as an Area Under the Curve (AUC) clot-assessment that estimates the time-averaged clot volume from ictus to end of treatment (EOT i.e. 24 hours after last dose) as AUC clot exposure and functional outcome (proportion 0-3 Modified Rankin Scale (mRS)).	24 hours after last dose
Patient Disposition: Home Days Over 365 Days Time From Ictus.	By group comparison of cumulative days at home during the 365 days post ictus.	During 365 days of follow-up
Patient Disposition: Patient Location at 365 Days Post Ictus (i.e., Good vs. Bad Location) (Adjusted)	Patient disposition: By group comparison of residential location at day 365 post ictus adjusted for baseline severity. Good locations refers to home and rehabilitation; and bad locations refers to acute care, long-term care and death.	Day 365
Dichotomized, Adjudicated, Cross-sectional Modified Rankin Scale (mRS) Score 0-3 vs. 4-6 180 Days Post Ictus (Adjusted)	Dichotomized, adjudicated, cross-sectional modified Rankin Scale (mRS) score 0-3 vs. 4-6 at 180 days post-ictus, adjusting for baseline (pre-randomization) variables used in covariate adaptive randomization as well as the clinically established severity variables IVH size and ICH location (lobar or deep). The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from: 0=No symptoms at all, 1=No significant disability, 2=Slight disability, 3=Moderate disability, 4=Moderately severe disability, 5=Severe disability and 6=death. Dichotomized scores are: 0-3=No symptoms to moderate disability requiring some assistance; 4-6=Moderately severe disability requiring complete assistance to death	Day 180
Dichotomized Extended Glasgow Outcome Scale (eGOS) Score UGR-US vs. LS-Death at 180 Days Post Ictus (Adjusted)	Dichotomized, cross-sectional extended Glasgow Outcome Scale (eGOS) score upper good recovery (UGR) through upper severe disability (US) vs. lower severe disability (LS) through death at 180 days post ictus, adjusting for baseline (pre-randomization) variables used in covariate adaptive randomization as well as the clinically established severity variables IVH size and ICH location (lobar or deep). The eGOS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored as: 1=Death, 2=Vegetative state, 3=Lower severe disability, 4=Upper severe disability, 5=Lower moderate disability, 6=Upper moderate disability, 7=Lower good recovery, 8=Upper good recovery. Dichotomous variable coding is as follows: 1=codes 4-8, 0=codes 1-3.	Day 180
Type and Intensity of ICU Management: ICU Days	By group comparison of cumulative number of days in the Intensive Care Unit (ICU) in a hospital	Up to 365 days
Type and Intensity of ICU Management: Hospital Days	By group comparison of total number of days in the hospital	Up to 365 days
EQ-VAS	By group comparison of EQ-VAS at day 365 post ictus. The EuroQol Visual Analogue Scale (EQ-VAS) is a self-reported measure of health status. It is a marked scale where subjects draw a line to indicate their health, with end points of 0 (the worst health you can imagine) and 100 (the best health you can imagine).	Day 365
EuroQol 5 Dimensional Scale (EQ-5D)	By group comparison of EQ-5D at day 365 post ictus. The EuroQol 5 Dimensional Scale (Eq-5D) is a self-reported measure of health status. It is arranged to assess domains related to mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. For each domain, codes were 1=no problems, 2=some problems, 3=extreme problems, and 9=unknown. Having a problem in at least 1 domain was coded as 1 (originally represented by 2 or 3) and no problems as 0 (originally represented by 1) .	Day 365

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality and Safety Events: First-week (Operative) Mortality	Mortality and Safety events: By group comparison of mortality within the first 7 days post randomization.	Day 7
Mortality and Safety Events: All Cause Mortality	By group comparison of mortality from all causes within the first 30 days post randomization.	Day 30
Mortality and Safety Events: Adjudicated Symptomatic Brain Bleeding Within 72 Hours After Last Dose	By group comparison of the percentage of subjects experiencing one or more adjudicated symptomatic brain bleeding events within the first 30 days post randomization.	72 hours after last dose
Mortality and Safety Events: Adjudicated Bacterial Brain Infection	By group comparison of the percentage of subjects experiencing one or more adjudicated brain bacterial infection events within the first 30 days post randomization.	Day 30
Mortality and Safety Events: Total Serious Adverse Events (SAE) at 30 Days	By group comparison of the total number of adjudicated serious adverse events that occurred within the first 30 days post randomization.	Day 30
Mortality and Safety Events: Summary of AE and SAE by MedDRA Code and Grouped by Organ System Within the First 30 Days Post Ictus	By group comparison of the total number of adjudicated adverse events (AE) and serious adverse events (SAE) across all coded organ systems that occurred within the first 30 days post ictus.	Day 30

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Genentech, Inc.; Emissary International LLC
• Investigators: Principal Investigator: Issam Awad, MD, University of Chicago; Study Chair: Daniel F. Hanley, MD, Johns Hopkins University; Principal Investigator: Mario Zuccarello, MD, University of Cincinnati

Publications and helpful links

General Publications

• Magid-Bernstein JR, Li Y, Cho SM, Piran PJ, Roh DJ, Gupta A, Shoamanesh A, Merkler A, Zhang C, Avadhani R, Montano N, Iadecola C, Falcone GJ, Sheth KN, Qureshi AI, Rosand J, Goldstein J, Awad I, Hanley DF, Kamel H, Ziai WC, Murthy SB. Cerebral Microbleeds and Acute Hematoma Characteristics in the ATACH-2 and MISTIE III Trials. Neurology. 2022 Mar 8;98(10):e1013-e1020. doi: 10.1212/WNL.0000000000013247. Epub 2021 Dec 22.
• Hanley DF, Thompson RE, Rosenblum M, Yenokyan G, Lane K, McBee N, Mayo SW, Bistran-Hall AJ, Gandhi D, Mould WA, Ullman N, Ali H, Carhuapoma JR, Kase CS, Lees KR, Dawson J, Wilson A, Betz JF, Sugar EA, Hao Y, Avadhani R, Caron JL, Harrigan MR, Carlson AP, Bulters D, LeDoux D, Huang J, Cobb C, Gupta G, Kitagawa R, Chicoine MR, Patel H, Dodd R, Camarata PJ, Wolfe S, Stadnik A, Money PL, Mitchell P, Sarabia R, Harnof S, Barzo P, Unterberg A, Teitelbaum JS, Wang W, Anderson CS, Mendelow AD, Gregson B, Janis S, Vespa P, Ziai W, Zuccarello M, Awad IA; MISTIE III Investigators. Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet. 2019 Mar 9;393(10175):1021-1032. doi: 10.1016/S0140-6736(19)30195-3. Epub 2019 Feb 7. Erratum In: Lancet. 2019 Apr 20;393(10181):1596.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2013
• Primary Completion (Actual): September 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: April 1, 2013
• First Submitted That Met QC Criteria: April 4, 2013
• First Posted (Estimate): April 9, 2013

Study Record Updates

• Last Update Posted (Actual): September 27, 2019
• Last Update Submitted That Met QC Criteria: September 26, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: intracerebral hemorrhage; ICH; minimally invasive surgery; rt-PA; brain hemorrhage
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator
• Other Study ID Numbers: NA_00080619; U01NS080824 (U.S. NIH Grant/Contract); ICH02 (Other Identifier: Other)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No