The PEERLESS II Study

• Sponsor: Inari Medical (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06055920
• Collaborator: (none)
• Enrollment: 1,200
• Locations: 33
• Arms: 2
• Anticipated Duration (Months): 32
• Patients Per Site: 36.4
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

This study is a prospective, multicenter, randomized controlled trial of the FlowTriever System plus anticoagulation compared to anticoagulation alone for intermediate-risk acute PE.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Embolism	Device: FlowTriever System; Drug: Anticoagulation Agents	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 1200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: PEERLESS II: RCT of FlowTriever vs. Anticoagulation Alone in Pulmonary Embolism
• Anticipated Study Start Date: Nov 1, 2023
• Anticipated Primary Completion Date: Jul 1, 2026
• Anticipated Study Completion Date: Jul 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: FlowTriever Mechanical thrombectomy for pulmonary embolism using the FlowTriever System.	Device: FlowTriever System; Mechanical Thrombectomy for pulmonary embolism
Active Comparator: Anticoagulation Commercially available/market approved anticoagulation medication including but not limited to: Heparin Sodium, Coumadin, Rivaroxaban, Apixaban, etc. Anticoagulants are a group of medications that decrease your blood's ability to clot.	Drug: Anticoagulation Agents; Commercially available/market approved anticoagulation medication including but not limited to: Heparin Sodium, Coumadin, Rivaroxaban, Apixaban, etc. Anticoagulants are a group of medications that decrease your blood's ability to clot.

Outcome Measures

Primary Outcome Measures

1. Composite clinical endpoint constructed as a win ratio, a hierarchy of the following, which are assessed post-randomization: [through discharge or 30 days, whichever is sooner / dyspnea at 48 hours]

   Clinical deterioration, defined by hemodynamic or respiratory worsening, through discharge or up to 30 days after randomization, whichever is sooner, or All-cause hospital re-admission by 30 days, or Bailout therapy, either after a deterioration or after documented failure to progress, through discharge or up to 30 days after randomization, whichever is sooner, or Dyspnea, by mMRC at the 48-hour visit

Secondary Outcome Measures

1. Composite clinical endpoint constructed as a win ratio hierarchy of the following three components, assessed post randomization: [up to 30 days]

   All-cause mortality, by 30 days, or Clinical deterioration defined by hemodynamic or respiratory worsening, through discharge or up to 30 days after randomization, whichever is sooner, or All-cause readmission, by 30 days

2. All-cause and PE-related mortality [At 30 and 90 days]

3. All-cause and PE-related readmissions [At 30 and 90 days]

4. Clinical deterioration [Through discharge or up to 30 days after randomization, whichever is sooner]

   defined by hemodynamic or respiratory worsening

5. Bailout therapy [Through discharge or up to 30 days after randomization, whichever is sooner]

   either after a deterioration or after documented failure to progress,

6. Major Bleeding, defined by the Bleeding Academic Research Consortium (BARC), level 3b, 3c, 5a, or 5b [At 30 and 90 days]

   3b: Overt bleeding plus hemoglobin drop of ≥ 5 g/dL (provided hemoglobin drop is related to bleed); cardiac tamponade, bleeding requiring surgical intervention for control (excluding dental/nasal/skin/hemorrhoid); bleeding requiring intravenous vasoactive agents 3c: Intracranial hemorrhage (does not include microbleeds or hemorrhagic transformation, does include intraspinal), subcategories confirmed by autopsy or imaging or lumbar puncture, intraocular bleed compromising vision. 5a: Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious 5b: Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation

7. Dyspnea severity by mMRC score [At the 48-hour, 1-month, and 3-month visits]

   0, no breathlessness except on strenuous exercise; 1, shortness of breath when hurrying on the level or walking up a slight hill; 2, walks slower than people of same age on the level because of breathlessness or has to stop to catch breath when walking at their own pace on the level; 3, stops for breath after walking ∼100 m or after few minutes on the level; and 4, too breathless to leave the house, or breathless when dressing or undressing

8. PE-related quality of life, by PEmb-QoL [At the 1- and 3-month visits]

   Pulmonary Embolism Quality of Life: (higher = better)

9. General health-related quality of life, by EQ-5D-5L [At the 1- and 3-month visits]

   Higher score = worse

10. 6-minute walk distance [At the 1-month visit]

11. RV/LV ratio [At the 48-hour visit]

12. Post-PE Impairment diagnosis (PPEI) [Through the 3-month visit]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age at enrollment ≥ 18 years

2. Objective evidence of a proximal filling defect in at least one main or lobar pulmonary artery, as confirmed by CTPA, pulmonary angiography, or other imaging modality

3. RV dysfunction, as defined as one or more of the following: RV/LV ratio ≥ 0.9 or RV dilation or hypokinesis

4. At least two additional risk factors, identified by at least one measure in two separate categories noted below:

1. Hemodynamic: i. SBP 90-100mmHg ii. Resting heart rate > 100 bpm b. Biomarker: i. Elevated* cardiac troponin (troponin I or troponin T, conventional or high sensitivity) ii. Elevated* BNP or NT-proBNP iii. Elevated venous lactate ≥2 mmol/L * Elevated, meaning at or above the upper limit of normal, per local standards for the assay used c. Respiratory: i. O2 saturation < 90% on room air ii. Supplemental O2 requirement ≥ 4 L/min iii. Respiratory rate ≥ 20 breaths/min iv. mMRC score > 0

1. Symptom onset within 14 days of confirmed PE diagnosis

2. Willing and able to provide informed consent

Exclusion Criteria:

1. Unable to be anticoagulated with heparin, enoxaparin or other parenteral antithrombin

2. Presentation with hemodynamic instability* that meets the high-risk PE definition in the 2019 ESC Guidelines1, including ANY of the following

3. Cardiac arrest OR

4. Systolic BP < 90 mmHg or vasopressors required to achieve a BP ≥ 90 mmHg despite adequate filling status, AND end-organ hypoperfusion OR

5. Systolic BP < 90 mmHg or systolic BP drop ≥ 40 mmHg, lasting longer than 15 min and not caused by new-onset arrhythmia, hypovolemia, or sepsis * Patients who are stable at time of screening or randomization (i.e., SBP ≥ 90 mmHg and adequate organ perfusion without catecholamine or vasopressor infusion) may be included despite initial presentation including temporary, low-dose catecholamines or vasopressors, or temporary fluid resuscitation.

6. Known sensitivity to radiographic contrast agents that, in the Investigator's opinion, cannot be adequately pre-treated

7. Imaging evidence or other evidence that suggests, in the opinion of the Investigator, the patient is not appropriate for catheter-based intervention (e.g., inability to navigate to target location, clot limited to segmental/subsegmental distribution, predominately chronic clot)

8. End stage medical condition with life expectancy < 3 months, as determined by the Investigator

9. Current participation in another drug or device study that, in the investigator's opinion, would interfere with participation in this study

10. Current or history of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic thromboembolic disease (CTED) diagnosis, per 2019 ESC Guidelines1

11. If objective testing was performed*, estimated RV systolic pressure > 70 mmHg on standard of care echocardiography * If clinical suspicion of acute-on-chronic PE, chronic obstruction, or chronic thromboembolism, echocardiographic estimated RVSP must be confirmed ≤70 mmHg to meet eligibility. Pressure assessment not required if Investigator attests to absence of such clinical suspicion

12. Administration of advanced therapies (thrombolytic bolus, thrombolytic drip/infusion, catheter-directed thrombolytic therapy, mechanical thrombectomy, or ECMO) for the index PE event within 30 days prior to enrollment

13. Ventricular arrhythmias refractory to treatment at the time of enrollment

14. Known to have heparin-induced thrombocytopenia (HIT)

15. Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being or that could prevent, limit, or confound the protocol-specified assessments). This includes a contraindication to use of FlowTriever System per local approved labeling

16. Subject is currently pregnant

17. Subject has previously completed or withdrawn from this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Division of Cardiovascular Disease	Birmingham	Alabama	United States	35205
2	Brookwood Medical Center	Birmingham	Alabama	United States	35243
3	Huntington Memorial Hospital	Pasadena	California	United States	91105
4	University of Colorado, Denver	Aurora	Colorado	United States	80045
5	HCA FL Largo Medical Center	Largo	Florida	United States	33770
6	Northwestern University	Chicago	Illinois	United States	60611
7	McLaren Greater Lansing	Lansing	Michigan	United States	48910
8	Sparrow Hospital	Lansing	Michigan	United States	48912
9	Metropolitan Heart & Vascular Institute	Coon Rapids	Minnesota	United States	55433
10	Valley Health	Ridgewood	New Jersey	United States	07450
11	Northwell Health	New York	New York	United States	10075
12	Jamaica Hospital	Queens	New York	United States	11418
13	Stony Brook University Hospital	Stony Brook	New York	United States	11794
14	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45219
15	Ohio State University - Wexner Medical Center	Columbus	Ohio	United States	43210
16	Mercy Hospital Springfield	Springfield	Ohio	United States	65804
17	AHN Saint Vincent Hospital	Erie	Pennsylvania	United States	16505
18	UPMC Harrisburg	Harrisburg	Pennsylvania	United States	17101
19	The University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
20	UPMC Heart and Vascular Institute	Pittsburgh	Pennsylvania	United States	15213
21	HCA Tristar	Brentwood	Tennessee	United States	37027
22	St. Thomas West	Nashville	Tennessee	United States	37205
23	Parkland Hospital	Dallas	Texas	United States	75235
24	Texas Tech / UMC	Lubbock	Texas	United States	79430
25	Baylor Scott & White - Temple	Temple	Texas	United States	76508
26	Inova Fairfax	Falls Church	Virginia	United States	22042
27	Carilion Roanoke	Roanoke	Virginia	United States	24014
28	University of Washington	Seattle	Washington	United States	98195
29	Providence Sacred Heart	Spokane	Washington	United States	99204
30	West Virginia University Ruby Memorial Hospital	Morgantown	West Virginia	United States	26506
31	Charité Campus Virchow Clinic - Klinik fuer Radiologie	Berlin		Germany
32	Klinikum rechts der Isar	Munich		Germany
33	Helios Kliniken Schwerin	Schwerin		Germany

Sponsors and Collaborators

• Inari Medical

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Inari Medical
• ClinicalTrials.gov Identifier: NCT06055920
• Other Study ID Numbers: 23-001
• First Posted: Sep 28, 2023
• Last Update Posted: Sep 28, 2023
• Last Verified: Sep 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Pulmonary Embolism; Embolism; Anticoagulants

Study Results

No Results Posted as of Sep 28, 2023