Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ..
AIMS: Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator. In preclinical and clinical studies in diabetes, trientine is associated with reduced LVH and fibrosis, and improved mitochondrial function and energy metabolism. Trientine was associated with improvements in cardiac structure and function in an open-label study in patients with HCM.
METHODS: The Efficacy and Mechanism of Trientine in Patients with Hypertrophic Cardiomyopathy (TEMPEST) trial is a multicentre, double-blind, parallel group, 1:1 randomised, placebo-controlled phase II trial designed to evaluate the efficacy and mechanism of action of trientine in patients with HCM. Patients with a diagnosis of HCM according to the European Society of Cardiology Guidelines and in New York Heart Association classes I-III are randomised to trientine or matching placebo for 52 weeks. Primary outcome is change in left ventricular (LV) mass indexed to body surface area, measured using cardiovascular magnetic resonance. Secondary efficacy objectives will determine whether trientine improves exercise capacity, reduces arrhythmia burden, reduces cardiomyocyte injury, improves LV and atrial function, and reduces LV outflow tract gradient. Mechanistic objectives will determine whether the effects are mediated by cellular or extracellular mass regression and improved myocardial energetics.
CONCLUSION: TEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM.
TRIAL REGISTRATION NUMBERS: NCT04706429 and ISRCTN57145331.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:109 |
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| Enthalten in: |
Heart (British Cardiac Society) - 109(2023), 15 vom: 12. Juli, Seite 1175-1182 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Farrant, John [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.07.2023 Date Revised 23.07.2023 published: Electronic ClinicalTrials.gov: NCT04706429 Citation Status MEDLINE |
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| doi: |
10.1136/heartjnl-2022-322271 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356409635 |
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| 245 | 1 | 0 | |a Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy |
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| 500 | |a Date Completed 14.07.2023 | ||
| 500 | |a Date Revised 23.07.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04706429 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ. | ||
| 520 | |a AIMS: Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator. In preclinical and clinical studies in diabetes, trientine is associated with reduced LVH and fibrosis, and improved mitochondrial function and energy metabolism. Trientine was associated with improvements in cardiac structure and function in an open-label study in patients with HCM | ||
| 520 | |a METHODS: The Efficacy and Mechanism of Trientine in Patients with Hypertrophic Cardiomyopathy (TEMPEST) trial is a multicentre, double-blind, parallel group, 1:1 randomised, placebo-controlled phase II trial designed to evaluate the efficacy and mechanism of action of trientine in patients with HCM. Patients with a diagnosis of HCM according to the European Society of Cardiology Guidelines and in New York Heart Association classes I-III are randomised to trientine or matching placebo for 52 weeks. Primary outcome is change in left ventricular (LV) mass indexed to body surface area, measured using cardiovascular magnetic resonance. Secondary efficacy objectives will determine whether trientine improves exercise capacity, reduces arrhythmia burden, reduces cardiomyocyte injury, improves LV and atrial function, and reduces LV outflow tract gradient. Mechanistic objectives will determine whether the effects are mediated by cellular or extracellular mass regression and improved myocardial energetics | ||
| 520 | |a CONCLUSION: TEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM | ||
| 520 | |a TRIAL REGISTRATION NUMBERS: NCT04706429 and ISRCTN57145331 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a cardiomyopathy, hypertrophic | |
| 650 | 4 | |a hypertrophic cardiomyopathy | |
| 650 | 4 | |a pharmacology, clinical | |
| 650 | 7 | |a Trientine |2 NLM | |
| 650 | 7 | |a SJ76Y07H5F |2 NLM | |
| 650 | 7 | |a Copper |2 NLM | |
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| 700 | 1 | |a Vaughan, Carly |e verfasserin |4 aut | |
| 700 | 1 | |a Reid, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Schmitt, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Garratt, Clifford |e verfasserin |4 aut | |
| 700 | 1 | |a Akhtar, Mohammed |e verfasserin |4 aut | |
| 700 | 1 | |a Mahmod, Masliza |e verfasserin |4 aut | |
| 700 | 1 | |a Neubauer, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Cooper, Robert M |e verfasserin |4 aut | |
| 700 | 1 | |a Prasad, Sanjay K |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Anvesha |e verfasserin |4 aut | |
| 700 | 1 | |a Valkovič, Ladislav |e verfasserin |4 aut | |
| 700 | 1 | |a Raman, Betty |e verfasserin |4 aut | |
| 700 | 1 | |a Ashkir, Zakariye |e verfasserin |4 aut | |
| 700 | 1 | |a Clayton, Dannii |e verfasserin |4 aut | |
| 700 | 1 | |a Baroja, Olatz |e verfasserin |4 aut | |
| 700 | 1 | |a Duran, Beatriz |e verfasserin |4 aut | |
| 700 | 1 | |a Spowart, Catherine |e verfasserin |4 aut | |
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| 700 | 1 | |a Naish, Josephine H |e verfasserin |4 aut | |
| 700 | 1 | |a Harrington, Chris |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Christopher A |e verfasserin |4 aut | |
| 700 | 0 | |a TEMPEST investigators |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Christopher |e investigator |4 oth | |
| 700 | 1 | |a Bedson, Emma |e investigator |4 oth | |
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| 700 | 1 | |a Dodd, Susanna |e investigator |4 oth | |
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| 700 | 1 | |a Mahmod, Masliza |e investigator |4 oth | |
| 700 | 1 | |a Naish, Josephine |e investigator |4 oth | |
| 700 | 1 | |a Neubauer, Stefan |e investigator |4 oth | |
| 700 | 1 | |a Prasad, Sanjay |e investigator |4 oth | |
| 700 | 1 | |a Schmitt, Matthias |e investigator |4 oth | |
| 700 | 1 | |a Williamson, Paula |e investigator |4 oth | |
| 700 | 1 | |a Columbine, Emma |e investigator |4 oth | |
| 700 | 1 | |a Piscitelli, Elisa |e investigator |4 oth | |
| 700 | 1 | |a Underhill, Suzanne |e investigator |4 oth | |
| 700 | 1 | |a Webster, Lynne |e investigator |4 oth | |
| 700 | 1 | |a Bedson, Emma |e investigator |4 oth | |
| 700 | 1 | |a Clayton, Danni |e investigator |4 oth | |
| 700 | 1 | |a Dodd, Susanna |e investigator |4 oth | |
| 700 | 1 | |a Jackson, Clare |e investigator |4 oth | |
| 700 | 1 | |a Kennedy, Keith |e investigator |4 oth | |
| 700 | 1 | |a Lawrence, Carly |e investigator |4 oth | |
| 700 | 1 | |a Low, Sophie |e investigator |4 oth | |
| 700 | 1 | |a Roberts, Stephanie |e investigator |4 oth | |
| 700 | 1 | |a Spowart, Catherine |e investigator |4 oth | |
| 700 | 1 | |a Williamson, Paula |e investigator |4 oth | |
| 700 | 1 | |a Harrington, Chris F |e investigator |4 oth | |
| 700 | 1 | |a Willis, Karl |e investigator |4 oth | |
| 700 | 1 | |a Mills, Craig |e investigator |4 oth | |
| 700 | 1 | |a Ahmad, Aisha |e investigator |4 oth | |
| 700 | 1 | |a Carpenter, Geoff |e investigator |4 oth | |
| 700 | 1 | |a George, Sherly |e investigator |4 oth | |
| 700 | 1 | |a Miller, Christopher |e investigator |4 oth | |
| 700 | 1 | |a Reid, Anna |e investigator |4 oth | |
| 700 | 1 | |a Schmitt, Matthias |e investigator |4 oth | |
| 700 | 1 | |a Garratt, Clifford |e investigator |4 oth | |
| 700 | 1 | |a Baroja, Olatz |e investigator |4 oth | |
| 700 | 1 | |a Clark, David |e investigator |4 oth | |
| 700 | 1 | |a Cotterell, David |e investigator |4 oth | |
| 700 | 1 | |a Duran, Beatriz |e investigator |4 oth | |
| 700 | 1 | |a Farrant, John |e investigator |4 oth | |
| 700 | 1 | |a George, Shiji |e investigator |4 oth | |
| 700 | 1 | |a Naish, Josephine |e investigator |4 oth | |
| 700 | 1 | |a Sarma, Jaydeep |e investigator |4 oth | |
| 700 | 1 | |a Westwell, Michelle |e investigator |4 oth | |
| 700 | 1 | |a Cooper, Robert |e investigator |4 oth | |
| 700 | 1 | |a Clarkson, Nichola |e investigator |4 oth | |
| 700 | 1 | |a Morgan, Maureen |e investigator |4 oth | |
| 700 | 1 | |a Mahmod, Masliza |e investigator |4 oth | |
| 700 | 1 | |a Neubauer, Stefan |e investigator |4 oth | |
| 700 | 1 | |a Akhtar, Mohammed |e investigator |4 oth | |
| 700 | 1 | |a Ashkir, Zakariye |e investigator |4 oth | |
| 700 | 1 | |a Rodigues, Liliana Da Silva |e investigator |4 oth | |
| 700 | 1 | |a Galley, Marion |e investigator |4 oth | |
| 700 | 1 | |a Jang, Injung |e investigator |4 oth | |
| 700 | 1 | |a Krasopoulos, Catherine |e investigator |4 oth | |
| 700 | 1 | |a Lamlum, Hanan |e investigator |4 oth | |
| 700 | 1 | |a Raman, Betty |e investigator |4 oth | |
| 700 | 1 | |a Valkovič, Ladislav |e investigator |4 oth | |
| 700 | 1 | |a Singh, Anvesha |e investigator |4 oth | |
| 700 | 1 | |a Dhutia, Harshil |e investigator |4 oth | |
| 700 | 1 | |a Gibson, Camilla |e investigator |4 oth | |
| 700 | 1 | |a Prasad, Sanjay |e investigator |4 oth | |
| 700 | 1 | |a Kirby, Kevin |e investigator |4 oth | |
| 700 | 1 | |a Halliday, Brian |e investigator |4 oth | |
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