Imperial College London
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DrLukeHoward

Faculty of Medicine, National Heart & Lung Institute

Professor of Practice (Cardiopulmonary Medicine)
 
 
 
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Contact

 

+44 (0)20 3313 3171l.howard Website

 
 
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Location

 

B3113Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wilkins:2021:10.1177/20458940211052823,
author = {Wilkins, M and McKie, M and Law, M and Roussakis, AA and Harbaum, L and Church, C and Coghlan, JG and Condliffe, R and Howard, L and Kiely, D and Lordan, J and Rothman, A and Suntharalingam, J and Toshner, M and Wort, J and Villar, SS},
doi = {10.1177/20458940211052823},
journal = {Pulmonary Circulation},
pages = {1--12},
title = {EXPRESS: Positioning Imatinib for Pulmonary Arterial Hypertension (PIPAH): A phase I/II design comprising dose finding and single arm efficacy Short title: Imatinib for PAH},
url = {http://dx.doi.org/10.1177/20458940211052823},
volume = {11},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pulmonary arterial hypertension is an unmet clinical need. Imatinib, a tyrosine kinase inhibitor, 200 to 400 mg daily reduces pulmonary artery pressure and increases functional capacity in this patient group, but is generally poorly tolerated at the higher dose. We have designed an open-label, single-arm clinical study to investigate whether there is a tolerated dose of imatinib that can be better targeted to patients who will benefit. The study consists of two parts. Part 1 seeks to identify the best tolerated dose of Imatinib in the range from 100 and up to 400 mg using a Bayesian Continuous Reassessment Method. Part 2 will measure efficacy after 24 weeks treatment with the best tolerated dose using a Simon’s two-stage design. The primary efficacy endpoint is a binary variable. For patients with a baseline pulmonary vascular resistance (PVR) >1000 dynes · s · cm−5, success is defined by an absolute reduction in PVR of ≥300 dynes · s · cm−5 at 24 weeks. For patients with a baseline PVR ≤1000 dynes · s · cm−5, success is a 30% reduction in PVR at 24 weeks. PVR will also be evaluated as a continuous variable by genotype as an exploratory analysis. Evaluating the response to that dose by genotype may inform a prospective biomarker-driven study.
AU  - Wilkins,M
AU  - McKie,M
AU  - Law,M
AU  - Roussakis,AA
AU  - Harbaum,L
AU  - Church,C
AU  - Coghlan,JG
AU  - Condliffe,R
AU  - Howard,L
AU  - Kiely,D
AU  - Lordan,J
AU  - Rothman,A
AU  - Suntharalingam,J
AU  - Toshner,M
AU  - Wort,J
AU  - Villar,SS
DO  - 10.1177/20458940211052823
EP  - 12
PY  - 2021///
SN  - 2045-8940
SP  - 1
TI  - EXPRESS: Positioning Imatinib for Pulmonary Arterial Hypertension (PIPAH): A phase I/II design comprising dose finding and single arm efficacy Short title: Imatinib for PAH
T2  - Pulmonary Circulation
UR  - http://dx.doi.org/10.1177/20458940211052823
UR  - https://journals.sagepub.com/doi/10.1177/20458940211052823
UR  - http://hdl.handle.net/10044/1/91997
VL  - 11
ER  -
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