# Sequential, Multiple Assignment, Randomized Trial in Severe Asthma Protocol (SMART-SA)

> **NIH NIH UG1** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $377,749

## Abstract

Summary/Abstract
The NHLBI Precision Interventions for Severe and Exacerbation Prone Asthma (PrecISE) Network will conduct
adaptive clinical trials in severe and exacerbation prone asthma. In Aim 1 we propose to form an international
consortium of four academic sites as a clinical center for PrecISE. The consortium will be led by the University
of California (UC) San Francisco asthma group (consortium and site PI: John Fahy) in partnership with three
other sites - the UC Davis Asthma Research Group (site PI: Nicholas Kenyon), the University of British
Columbia Asthma Research Group (site PI: Mark FitzGerald), and the University of Leicester Asthma
Research Group (site PI: Chris Brightling). All are academic sites highly experienced in conducting clinical
studies in severe asthma, and all have made important contributions to current knowledge about disease
mechanisms in asthma. Together, we propose to quickly recruit 100 patients with severe and exacerbation
prone asthma for enrollment in PrecISE, and we will implement each network-wide protocol approved by the
Steering Committee. In Aim 2 we propose that PrecISE should adopt the sequential multiple assignment
randomized trial (SMART) approach to conduct adaptive trials in subgroups of asthmatics defined by the
presence or absence of systemic IL6 inflammation or systemic eosinophilia. We specifically propose three
clinical trials, each in approximately one third of the 800 person PrecISE cohort. Trial #1 will sequentially test
the efficacy of Tocilizumab and Anakinra in IL6-high asthma. Trial #2 will sequentially test the efficacy of
Mepolizumab and Dupilumab in reversing airflow obstruction in patients with “type 2-high” asthma. Trial #3 will
sequentially test the efficacy of Doxycycline and steroid withdrawal on asthma control in patients with “type 2-
low” asthma. In all of these trials, our overarching goal is to advance precision medicine for patients with more
severe forms of asthma.

## Key facts

- **NIH application ID:** 9984892
- **Project number:** 5UG1HL139106-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** John V Fahy
- **Activity code:** UG1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,749
- **Award type:** 5
- **Project period:** 2017-09-23 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984892

## Citation

> US National Institutes of Health, RePORTER application 9984892, Sequential, Multiple Assignment, Randomized Trial in Severe Asthma Protocol (SMART-SA) (5UG1HL139106-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9984892. Licensed CC0.

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