FORWARD: Functional Outcomes in Real-World Treatment And Revascularization of Non-dominant and Distal M2 Occlusions

The objective of this study is to collect safety and effectiveness data on the Penumbra System reperfusion catheters in participants with isolated primary non-dominant and distal M2 occlusions who undergo endovascular mechanical thrombectomy (EVT). Additionally, this study aims to observe characteristics and outcomes of participants treated with medical management (MM) alone and those who receive EVT + MM per current medical practice.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke; Acute Ischemic Stroke (AIS) Related to a Distal Occlusion
• Intervention / Treatment: Other: Medical Management; Device: Endovascular Thrombectomy

Detailed Description

FORWARD is a prospective, multicenter, observational study that will be conducted internationally.

Participants who satisfy all inclusion criteria and none of the exclusion criteria will be eligible for enrollment. They will receive treatment according to the physicians' clinical judgement per standard of care at their institution.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Madeline Turtle; Phone Number: 260-224-8231; Email: MTurtle@PENUMBRAINC.COM
• Study Contact Backup: Name: Jennifer Jelf; Phone Number: 510-440-5719; Email: jjelf@penumbrainc.com

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • Recruiting
      • Fort Sanders Regional Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants experiencing acute ischemic stroke (AIS) due to a primary M2 occlusion in the vertical segment or post-bifurcation in the non-dominant or co-dominant branch of the horizontal segment.

Description

Inclusion Criteria:

1. Participant age ≥ 18
2. Participant experiencing acute ischemic stroke due to a confirmed primary M2 occlusion in the vertical segment or post-bifurcation in the non-dominant or co-dominant branch of the horizontal segment
3. NIHSS ≥5 or NIHSS 3-4 with disabling symptoms
4. Pre-stroke mRS 0-1
5. For participants undergoing thrombectomy: Planned first-line treatment with Penumbra System reperfusion catheters
6. Informed consent obtained per Institutional Review Board/Ethics Committee requirements

Exclusion Criteria:

1. Any stenosis or occlusion in the ICA origin requiring treatment during the procedure or within the 90-day follow-up period.
2. Known multiple occlusions
3. Secondary M2 occlusion
4. Known or high suspicion of underlying ICAD as the cause of the M2 occlusion
5. Current hospitalization at time of stroke onset and/or any comorbid disease or condition expected to compromise survival or ability to complete follow-up assessments through 90 days
6. Currently participating in an investigational (drug, device, etc.) clinical trial that will influence the endovascular procedure or acute treatment. Participants in secondary prevention, observational, natural history and/or epidemiological studies are eligible.
7. Other medical, behavioral, or psychological conditions that in the opinion of the Investigator could limit the ability to participate in the study, including compliance with follow-up requirements, or that could impact the scientific integrity of the study

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Medical Management	Other: Medical Management; All medical management treatment will follow established guidelines for the care of stroke patients. All medical treatments and supportive care will be administered following each participating hospital's routine practice and in accordance with the Instructions for Use for any medication administered.
Endovascular Thrombectomy plus Medical Management	Other: Medical Management; All medical management treatment will follow established guidelines for the care of stroke patients. All medical treatments and supportive care will be administered following each participating hospital's routine practice and in accordance with the Instructions for Use for any medication administered.; Device: Endovascular Thrombectomy; Patients will undergo endovascular thrombectomy plus medical management. Patients will be treated with the Penumbra System Reperfusion Catheters. Perioperative and postoperative management will follow established guidelines for the care of stroke patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in NIHSS at 24 hours	The National Institutes of Health Stroke Scale (NIHSS) is a standardized neurological examination tool used to measure the severity of a stroke. The scale ranges from 0 to 42, with higher scores indicating greater impairment.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day Modified Rankin Scale (mRS)	The modified Rankin Scale (mRS) is used to measure the degree of disability or dependence in daily activities in people who have experienced a stroke. Scores range from no symptoms (0) to death (6), with higher scores indicating greater severity.	90 Days
Reperfusion measures, quantified as proportion of participants with a final mTICI 2b or higher after all treatment		Treatment/Procedure
90-day NIHSS	The National Institutes of Health Stroke Scale (NIHSS) is a standardized neurological examination tool used to measure the severity of a stroke. The scale ranges from 0 to 42, with higher scores indicating greater impairment.	90 Days
Quality of Life, as measured by Barthel Index	The Barthel Index is a 0-100 point scale used to measure a person's functional independence in daily activities. The index rates 10 items, including feeding, bathing, grooming, dressing, bowel/bladder control, toilet use, transfers, mobility, and stair use. Higher scores indicate greater independence, while lower scores signify higher dependency on caregivers.	90 Days
Quality of Life, as measured by Neuro-QoL	Neuro-QoL is a set of patient-reported outcome measures designed to assess health-related quality of life across physical, mental, and social domains relevant to individuals with neurological conditions. It uses calibrated item banks and short forms to measure constructs such as mobility, cognitive function, emotional/behavioral health, fatigue, and social participation.	90 Days
Quality of Life, as measured by Canadian Outcome Scale for Minor Stroke (COSMOS)	COSMOS is a 7-point scale ranging from 0 (no symptoms) to 6 (loss of independence for an instrumental or basic activity of daily living or worse), which accounts for performance limitations and losses of a person's hobbies or passions and of their employment, educational, service, or caregiving pursuits, besides just activities of daily living.	90 Days
Safety events of interest		Treatment, Procedure (if applicable), 24 Hours, Discharge and/or 7 Days, 90 Days
Treatment method per the physician's clinical judgment		Baseline

Collaborators and Investigators

• Sponsor: Penumbra Inc.
• Investigators: Principal Investigator: Alejandro Spiotta, MD, Medical University of South Carolina; Principal Investigator: Nitin Goyal, MD, University of Tennessee Health Science Center/Semmes Murphey Clinic

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: July 8, 2026
• First Submitted That Met QC Criteria: August 5, 2026
• First Posted (Actual): August 6, 2026

Study Record Updates

• Last Update Posted (Actual): August 6, 2026
• Last Update Submitted That Met QC Criteria: August 5, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Professional Practice; Organization and Administration; Health Services Administration; Practice Management; Practice Management, Medical
• Other Study ID Numbers: 33727

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: No