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.

Public Health Relevance

This application is in response to the NHLBI's Precision Interventions for Severe and/or Exacerbation Prone Asthma (PrecISE) Network. We propose to lead a clinical center that is a consortium of four academic sites, and we will conduct sequential multiple assignment, randomized trials in severe asthma with the overarching goal of improving care for patients with severe forms of asthma.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Research Cooperative Agreements - Single Project (UG1)
Project #
1UG1HL139106-01
Application #
9405804
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Noel, Patricia
Project Start
2017-09-23
Project End
2023-06-30
Budget Start
2017-09-23
Budget End
2018-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118