Impact of Acute iTTP Therapies on Long Term Neurologic and Cognitive Outcomes in iTTP Survivors (NeST)

1. We expect to find that the silent cerebral infarct (SCI) rate is two fold higher in patients treated without caplacizumab. We also expect to find that the rate of mild and major cognitive impairment in patients treated with caplacizumab within 3 days of starting plasma exchange will be lower than patients treated without caplacizumab.
2. We expect that the differences in cognitive impairment in cases (caplacizumab) versus controls (no caplacizumab) will persist on serial evaluation 1 year later. We also expect that there will be differences in these groups even after adjusting for time since episode and severity of presentation.
3. We expect to find that SCI and cognitive impairment is associated with worse scores on the health related quality of life instrument (SF-36)
4. Based on studies in non-TTP populations, we expect to find that the rate of incident stroke over the period of follow up is at least 2 fold higher in patients that have SCI compared with patients who do not have SCI

Study Overview

• Status: Not yet recruiting
• Conditions: Immune Thrombotic Thrombocytopenia
• Intervention / Treatment: Drug: Caplacizumab

• Study Type: Observational
• Enrollment (Estimated): 116

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Groveport, Ohio, United States, 43125
      • USTMA
      • Contact: Clare Martin; Phone Number: 614-999-4900; Email: Clare@ustma.org

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adults with iTTP

Description

Inclusion Criteria:

1. Age >= 18 years
2. Confirmed iTTP based on ADAMS13 activity < 10 % (or 10-20% with positive inhibitor or antibody) during an acute iTTP episode
3. Only 1 episode of iTTP that was treated with plasma exchange and caplacizumab started within 3 days of diagnosis (or if more than 1 episode, then all episodes treated with plasma exchange and caplacizumab started within 3 days of diagnosis)

Exclusion Criteria:

1. Any contraindication for MRI (metallic implants, shrapnel, MRI incompatible stents, etc)
2. Unable to speak, read or understand instructions in English (for NIH ToolBox)
3. Combination of iTTP episodes treated without caplacizumab or with caplacizumab.
4. Caplacizumab started at >= 4 days from diagnosis or for refractory iTTP

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Controls
Cases	Drug: Caplacizumab; Early Caplacizumab use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Silent cerebral infarction	Silent cerebral infarction (primary endpoint) - SCI is derived from quantitation (number and total volume) of ischemic (infarct-like) lesions shown as foci of T2 and FLAIR hyperintensity. SCI is diagnosed if the participant has an infarct like lesion, at least 3 mm, with normal neurologic examination or an abnormality on examination that is not explained by the location of the brain lesion. We have assembled a panel of 3 neuroradiologists headed by Dr. Doris Lin. Each MRI will be read by 2 radiologists. A third reviewer will serve as a tie breaker in case of disagreement.	12 months
Cognitive impairment	Cognitive impairment (co-primary endpoint) - measured using NIH ToolBox Cognition Battery. Mild and major cognitive impairment are defined as T scores that are 1-2 SD below mean and > 2SD below mean for any domain, respectively	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression scores on BDI-II		12 months
SF-36 scores for quality of life		12 months
Patient reported cognitive performance	(PROMIS Cognitive Function - Short form 8a)	12 months

Collaborators and Investigators

• Sponsor: US Thrombotic Microangiopathy Alliance

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: April 4, 2024
• First Submitted That Met QC Criteria: April 4, 2024
• First Posted (Actual): April 10, 2024

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: TTP; Cognitive impairment; aTTP; iTTP
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Cytopenia; Thrombocytopenia
• Other Study ID Numbers: P400

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: No