Chronic Heart FailureCOVERT-HFNCT02541773
Novel Vascular Biomarkers Behaviour and Clinical Value in Heart Failure and CRT
An observational study of Chronic Heart Failure, run by University Hospitals Coventry and Warwickshire NHS Trust at 1 site in United Kingdom.
Trial summary
The purpose of this study is to understand the behaviour of certain blood markers in patients with heart failure who undergo a cardiac device implantation procedure called cardiac resynchronization therapy (CRT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Heart Failure
- What is being tested?
- Cardiac Resynchronisation Therapy
- Type of treatment
- Medical device
- How many people
- 58 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2013to Jun 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Chronic heart failure patients who have been referred for and meet national criteria for Cardiac Resynchronization Therapy implants
Who may be able to join
- Age > 18 years
- Left ventricular ejection fraction ≤35% on echocardiography
- NYHA Class III/IV symptoms or milder symptoms with:
- NYHA I (LVEF <35% and QRS>150msec on resting ECG)
- NYHA II (LVEF <35% with either QRS>150msec or QRS 120-149msec with Left Bundle Branch Block on resting ECG)
- Optimal medical therapy for heart failure that the patient tolerates (ACEi, Beta-Blocker, Mineralocorticoid) for > 3 months
- QRS duration ≥120-149msec with LBBB on resting ECG or QRS duration >150msec on resting ECG
- Patient consent to participation in the study
Who cannot join
- Acute heart failure decompensation < 6/52 before implant
- Significant cognitive impairment
- Acute coronary syndrome < 6/52 before implant
- Chronic kidney disease stage V (requiring dialysis)
- Terminal illness with likely survival < 1 year after implant
- Post Procedure Exclusions:
- 1. Failure of procedure (e.g. coronary sinus anatomy) 2. Complication resulting in poor/ none biventricular pacing (e.g. phrenic nerve stimulation, lead displacement/ damage)
- -
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospital Coventry and Warwickshire
Coventry, Warwickshire, CV2 2DX
About this study
Official title: The Characterisation of Vascular Biomarkers Before and After Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure and Their Role in Predicting Response
The purpose of this study is to understand the behaviour of certain blood markers in patients with heart failure who undergo a cardiac device implantation procedure called cardiac resynchronization therapy (CRT). CRT is an effective treatment for heart failure, but up to 30% of people do not respond and have poor outcomes (1,2). Despite extensive investigation, identifying these patients continues to be a challenge. The study intends to describe the changes in these blood markers before and after CRT and to examine any potential clinical value.
The idea behind the study is that these blood markers alter in heart failure and change with CRT implantation. Furthermore the pattern of marker expression before implant and after may predict response and outcome.
Read the detailed description
Study Design A prospective, non-randomised, self-control study of unselected heart failure patients undergoing CRT implantation, all recruited within two years All participants having CRT implantation at University Hospital Coventry and Warwickshire will be screened using the eligibility criteria (outlined below).
Participants will have three assessments within six months (baseline, 6 weeks and 6 months approximately). All visits coincide with routine clinical visits for CRT implantation and interrogation. Assessments at all three time points will include clinical data (including New York Heart Association functional class), quality of life measurements (Minnesota Living with Heart Failure questionnaire), echocardiography data (left ventricular volumetric assessment, ejection fraction), electrocardiograph, functional capacity (6 minute-walk test) and body composition assessment (air displacement). Peripheral blood samples will be taken to examine novel vascular biomarkers and to examine renal function, full blood count, diabetic control (HBA1c - only diabetics) and Brain Natruetic Peptide. Coronary sinus samples will be taken for novel vascular biomarkers in a small proportion of the cohort.
Blood Sampling and Storage
Participants are asked to starve for two hours and rest for one hour before blood sampling. Coronary sinus blood sampling occurs at the time of coronary sinus cannulation before contrast is injected. Blood samples (serum/plasma) are taken in citrate and EDTA tubes. The samples stand at room temperature for a minimum of 30 minutes and undergo centrifugation within an hour. Centrifugation (3500rpm for 10 minutes) occurs at room temperature. Samples are then stored in -80 freezer.
Laboratory Analysis
Samples will undergo final analysis at the University of Warwick and Kings College London. Novel vascular biomarkers of heart failure that exist as proteins in the serum will be analysed using enzyme-linked immunosorbent assay (ELISA) techniques previously outlined in publications (3-6). The specific novel vascular biomarkers represent different aspects of adverse ventricular remodelling; myocardial stress [Growth Differentiation Factor-15] and extracellular remodelling [Matrix Metalloproteinases -2 \& -9, Aminoterminal Propeptides of Type I Collagen (PINP), Aminoterminal Propeptides of Type III Collagen (PIIINP), Carboxy-Terminal Telopeptide of Type I Collagen (CITP)] (4-7). These markers will undergo quantification using ELISA techniques that have previously described in the literature (8, 9).
Micro Ribonucleic Acids (miRNA) profiling will be undertaken in coronary sinus and peripheral samples and will be compared to those taken after CRT implantation. Responders will be compared to non-responders to determine variation in profile between these two distinct groups. Profiling and quantification will be performed as described in previous publications (10-12). Specific cardiac miRNA will be pre-selected to screen and quantify, especially those have already been proven to have altered expression in heart failure (13-16).
Device Implantation
CRT devices (pacemaker of defibrillator) are implanted by two independent operators at our single centre in a standard fashion. CRT is implanted traditionally in the left deltopectoral groove. Venous access is via the cephalic>axillary>subclavian veins (all operators can cannulate either vein based on individual patient). Right ventricular lead for the majority of patients will be implanted at the right ventricular apex. Right atrial leads will be planned to be implanted in the right atrial appendage. Patients in permanent Atrial Fibrillation will not have a right atrial lead implanted. Coronary sinus will be cannulated and angiography performed to roadmap anatomy for lead deployment site. The most lateral position will be favoured in a basal/ mid-cavity position. At the point of coronary sinus cannulation blood samples (plasma/serum will be taken). Post procedure patients undergo targeted echocardiography and a chest x-ray film. Post procedure on the day of implant patients will undergo CRT interrogation and optimisation of programming.
Echocardiography
A focused echocardiographic study assessing the left ventricle will be performed to the recommended international standard (17). The left ventricular systolic and diastolic function will be fully assessed. Volumetric assessment will be performed using Simpson's method (17). Diastolic function will be assessed by performing volumetric assessment of the left atrium, measuring pulse wave inflow of ventricular filling and TDI of the lateral and septal walls [apical 4 chamber]. All scans will be performed on the departmental machines [GE systems, Vivid 7] and by the same operator. Scans will be performed independently and previous scans will not have been reviewed before this scan. Full analysis will be conducted once all scans have been performed.
Inter- and Intra-Observer Variability Echocardiography Study
An inter- and intra-observer variability study will be performed to ensure standardisation of echocardiographic examinations. Twenty percent of echocardiograms will be randomly selected to have measurements and conclusions reviewed. An independent cardiologist/ cardiac physiologist (accredited by the British Society of Echocardiography) will be blinded to selected echocardiograms and will validate reporting and measurements of these examinations.
Body Composition
Air-displacement plethysmography (Bodpod) is an easily accessible and safe tool to measure body composition (18). The assessment is reproducible and is comparable to other measures of body composition (18). The major advantage of Bodpod is that it is safe for patients who have had a CRT implanted. The University of Warwick and University Hospital Coventry and Warwickshire (UHCW) has one of the few facilities in their Human Metabolic Unit to perform Bodpod.
- Conditions
- Chronic Heart Failure
- Being tested
- Cardiac Resynchronisation Therapy
- Keywords
- Chronic Heart Failure, Cardiac Resynchronization Therapy, Vascular Biomarker, miRNA, Extracellular Matrix, Brain Natruetic Peptide, Growth Degradation Factor-15, Body Composition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiac Resynchronisation TherapyDevice
Routine implantation of CRT - part of standard of care
| Study group | Role | What they receive |
|---|---|---|
| Chronic Heart Failure Patients | Undergoing CRT implantation, all will be observed for 6 months and will be defined at the end of the observation period as responder or non-responder Receives: Device: Cardiac Resynchronisation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response
Two of three criteria must be fulfilled to be defined as a clinical response:
- New York Heart Association (NYHA) > 1 class reduction from baseline
- Minnesota Living with Heart Failure Questionnaire (MLHFQ) score < 5 from baseline
- Six minute walk test (6MWT) increase in baseline distance by 10%
Mortality or heart transplantation within 6 months of implant will be defined as a non-response.
Measured: 6 months
Secondary outcomes (2)
Major Adverse Cardiovascular Outcomes
Composite score of all-cause mortality and first heart failure hospitalisation (admission requiring intravenous diuretics)
Measured: 12 months
Echocardiographic Response
≥15% reduction in left ventricular end-systolic volume
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2015 (estimated)
- Study startNov 2013
- Primary completionJun 2016 (estimated)
- Study completionJun 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Chronic Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospitals Coventry and Warwickshire NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Medtronic
- Responsible party
- Principal investigator, Dr Christopher McAloon, University Hospitals Coventry and Warwickshire NHS Trust
- Investigators
- Faizel Osman, MD FRCP FESC, Principal investigator, University Hospital Coventry and Warwickshire
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02541773
- Sponsor's protocol ID
- version 10 20 Jan 2016
- Acronym
- COVERT-HF
- Status last verified
- Sep 2015
- First submitted
- 2 Sep 2015
- Last updated
- 9 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L; Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005 Apr 14;352(15):1539-49. doi: 10.1056/NEJMoa050496. Epub 2005 Mar 7.
PubMed 15753115Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM; Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004 May 20;350(21):2140-50. doi: 10.1056/NEJMoa032423.
PubMed 15152059Garcia-Bolao I, Macias A, Lopez B, Gonzalez A, Gavira JJ, Azcarate P, Alegria E, Diez J. A biomarker of myocardial fibrosis predicts long-term response to cardiac resynchronization therapy. J Am Coll Cardiol. 2006 Jun 6;47(11):2335-7. doi: 10.1016/j.jacc.2006.03.012. Epub 2006 May 16. No abstract available.
PubMed 16750706Garcia-Bolao I, Lopez B, Macias A, Gavira JJ, Azcarate P, Diez J. Impact of collagen type I turnover on the long-term response to cardiac resynchronization therapy. Eur Heart J. 2008 Apr;29(7):898-906. doi: 10.1093/eurheartj/ehn098. Epub 2008 Mar 10.
PubMed 18334474Hessel MH, Bleeker GB, Bax JJ, Henneman MM, den Adel B, Klok M, Schalij MJ, Atsma DE, van der Laarse A. Reverse ventricular remodelling after cardiac resynchronization therapy is associated with a reduction in serum tenascin-C and plasma matrix metalloproteinase-9 levels. Eur J Heart Fail. 2007 Oct;9(10):1058-63. doi: 10.1016/j.ejheart.2007.07.007. Epub 2007 Aug 28.
PubMed 17728181Umar S, Bax JJ, Klok M, van Bommel RJ, Hessel MH, den Adel B, Bleeker GB, Henneman MM, Atsma DE, van der Wall EE, Schalij MJ, van der Laarse A. Myocardial collagen metabolism in failing hearts before and during cardiac resynchronization therapy. Eur J Heart Fail. 2008 Sep;10(9):878-83. doi: 10.1016/j.ejheart.2008.06.019. Epub 2008 Sep 2.
PubMed 18768351Foley PW, Stegemann B, Ng K, Ramachandran S, Proudler A, Frenneaux MP, Ng LL, Leyva F. Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy. Eur Heart J. 2009 Nov;30(22):2749-57. doi: 10.1093/eurheartj/ehp300. Epub 2009 Aug 7.
PubMed 19666898Lewandowski KC, Komorowski J, Mikhalidis DP, Bienkiewicz M, Tan BK, O'Callaghan CJ, Lewinski A, Prelevic G, Randeva HS. Effects of hormone replacement therapy type and route of administration on plasma matrix metalloproteinases and their tissue inhibitors in postmenopausal women. J Clin Endocrinol Metab. 2006 Aug;91(8):3123-30. doi: 10.1210/jc.2005-2789. Epub 2006 May 16.
PubMed 16705077Randeva HS, Lewandowski KC, Komorowski J, Murray RD, O'Callaghan CJ, Hillhouse EW, Stepien H, Shalet SM. Growth hormone replacement decreases plasma levels of matrix metalloproteinases (2 and 9) and vascular endothelial growth factor in growth hormone-deficient individuals. Circulation. 2004 May 25;109(20):2405-10. doi: 10.1161/01.CIR.0000129763.51060.77. Epub 2004 May 3.
PubMed 15123527Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010 Sep 17;107(6):810-7. doi: 10.1161/CIRCRESAHA.110.226357. Epub 2010 Jul 22.
PubMed 20651284Willeit P, Zampetaki A, Dudek K, Kaudewitz D, King A, Kirkby NS, Crosby-Nwaobi R, Prokopi M, Drozdov I, Langley SR, Sivaprasad S, Markus HS, Mitchell JA, Warner TD, Kiechl S, Mayr M. Circulating microRNAs as novel biomarkers for platelet activation. Circ Res. 2013 Feb 15;112(4):595-600. doi: 10.1161/CIRCRESAHA.111.300539. Epub 2013 Jan 2.
PubMed 23283721Zampetaki A, Mayr M. Analytical challenges and technical limitations in assessing circulating miRNAs. Thromb Haemost. 2012 Oct;108(4):592-8. doi: 10.1160/TH12-02-0097. Epub 2012 May 25.
PubMed 22627831Romaine SP, Tomaszewski M, Condorelli G, Samani NJ. MicroRNAs in cardiovascular disease: an introduction for clinicians. Heart. 2015 Jun;101(12):921-8. doi: 10.1136/heartjnl-2013-305402. Epub 2015 Mar 26.
PubMed 25814653Marfella R, Di Filippo C, Potenza N, Sardu C, Rizzo MR, Siniscalchi M, Musacchio E, Barbieri M, Mauro C, Mosca N, Solimene F, Mottola MT, Russo A, Rossi F, Paolisso G, D'Amico M. Circulating microRNA changes in heart failure patients treated with cardiac resynchronization therapy: responders vs. non-responders. Eur J Heart Fail. 2013 Nov;15(11):1277-88. doi: 10.1093/eurjhf/hft088. Epub 2013 Jun 4.
PubMed 23736534Vogel B, Keller A, Frese KS, Leidinger P, Sedaghat-Hamedani F, Kayvanpour E, Kloos W, Backe C, Thanaraj A, Brefort T, Beier M, Hardt S, Meese E, Katus HA, Meder B. Multivariate miRNA signatures as biomarkers for non-ischaemic systolic heart failure. Eur Heart J. 2013 Sep;34(36):2812-22. doi: 10.1093/eurheartj/eht256. Epub 2013 Jul 17.
PubMed 23864135
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Characterisation of Vascular Biomarkers Before and After Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure and Their Role in Predicting Response
- ClinicalTrials.gov ID
- NCT02541773
- Acronym / sponsor ID
- COVERT-HF / version 10 20 Jan 2016
- Conditions
- Chronic Heart Failure
- Keywords
- Chronic Heart Failure, Cardiac Resynchronization Therapy, Vascular Biomarker, miRNA, Extracellular Matrix, Brain Natruetic Peptide, Growth Degradation Factor-15, Body Composition
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- University Hospitals Coventry and Warwickshire NHS TrustUniversity, hospital or other
- Collaborators
- Medtronic
- Study start
- Nov 2013
- Primary completion
- Jun 2016 (estimated)
- Study completion
- Jun 2016 (estimated)
- First posted
- 4 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to understand the behaviour of certain blood markers in patients with heart failure who undergo a cardiac device implantation procedure called cardiac resynchronization therapy (CRT). CRT is an effective treatment for heart failure, but up to 30% of people do not respond and have poor outcomes (1,2). Despite extensive investigation, identifying these patients continues to be a challenge. The study intends to describe the changes in these blood markers before and after CRT and to examine any potential clinical value.
The idea behind the study is that these blood markers alter in heart failure and change with CRT implantation. Furthermore the pattern of marker expression before implant and after may predict response and outcome.
Detailed description
Study Design A prospective, non-randomised, self-control study of unselected heart failure patients undergoing CRT implantation, all recruited within two years All participants having CRT implantation at University Hospital Coventry and Warwickshire will be screened using the eligibility criteria (outlined below).
Participants will have three assessments within six months (baseline, 6 weeks and 6 months approximately). All visits coincide with routine clinical visits for CRT implantation and interrogation. Assessments at all three time points will include clinical data (including New York Heart Association functional class), quality of life measurements (Minnesota Living with Heart Failure questionnaire), echocardiography data (left ventricular volumetric assessment, ejection fraction), electrocardiograph, functional capacity (6 minute-walk test) and body composition assessment (air displacement). Peripheral blood samples will be taken to examine novel vascular biomarkers and to examine renal function, full blood count, diabetic control (HBA1c - only diabetics) and Brain Natruetic Peptide. Coronary sinus samples will be taken for novel vascular biomarkers in a small proportion of the cohort.
Blood Sampling and Storage
Participants are asked to starve for two hours and rest for one hour before blood sampling. Coronary sinus blood sampling occurs at the time of coronary sinus cannulation before contrast is injected. Blood samples (serum/plasma) are taken in citrate and EDTA tubes. The samples stand at room temperature for a minimum of 30 minutes and undergo centrifugation within an hour. Centrifugation (3500rpm for 10 minutes) occurs at room temperature. Samples are then stored in -80 freezer.
Laboratory Analysis
Samples will undergo final analysis at the University of Warwick and Kings College London. Novel vascular biomarkers of heart failure that exist as proteins in the serum will be analysed using enzyme-linked immunosorbent assay (ELISA) techniques previously outlined in publications (3-6). The specific novel vascular biomarkers represent different aspects of adverse ventricular remodelling; myocardial stress [Growth Differentiation Factor-15] and extracellular remodelling [Matrix Metalloproteinases -2 \& -9, Aminoterminal Propeptides of Type I Collagen (PINP), Aminoterminal Propeptides of Type III Collagen (PIIINP), Carboxy-Terminal Telopeptide of Type I Collagen (CITP)] (4-7). These markers will undergo quantification using ELISA techniques that have previously described in the literature (8, 9).
Micro Ribonucleic Acids (miRNA) profiling will be undertaken in coronary sinus and peripheral samples and will be compared to those taken after CRT implantation. Responders will be compared to non-responders to determine variation in profile between these two distinct groups. Profiling and quantification will be performed as described in previous publications (10-12). Specific cardiac miRNA will be pre-selected to screen and quantify, especially those have already been proven to have altered expression in heart failure (13-16).
Device Implantation
CRT devices (pacemaker of defibrillator) are implanted by two independent operators at our single centre in a standard fashion. CRT is implanted traditionally in the left deltopectoral groove. Venous access is via the cephalic>axillary>subclavian veins (all operators can cannulate either vein based on individual patient). Right ventricular lead for the majority of patients will be implanted at the right ventricular apex. Right atrial leads will be planned to be implanted in the right atrial appendage. Patients in permanent Atrial Fibrillation will not have a right atrial lead implanted. Coronary sinus will be cannulated and angiography performed to roadmap anatomy for lead deployment site. The most lateral position will be favoured in a basal/ mid-cavity position. At the point of coronary sinus cannulation blood samples (plasma/serum will be taken). Post procedure patients undergo targeted echocardiography and a chest x-ray film. Post procedure on the day of implant patients will undergo CRT interrogation and optimisation of programming.
Echocardiography
A focused echocardiographic study assessing the left ventricle will be performed to the recommended international standard (17). The left ventricular systolic and diastolic function will be fully assessed. Volumetric assessment will be performed using Simpson's method (17). Diastolic function will be assessed by performing volumetric assessment of the left atrium, measuring pulse wave inflow of ventricular filling and TDI of the lateral and septal walls [apical 4 chamber]. All scans will be performed on the departmental machines [GE systems, Vivid 7] and by the same operator. Scans will be performed independently and previous scans will not have been reviewed before this scan. Full analysis will be conducted once all scans have been performed.
Inter- and Intra-Observer Variability Echocardiography Study
An inter- and intra-observer variability study will be performed to ensure standardisation of echocardiographic examinations. Twenty percent of echocardiograms will be randomly selected to have measurements and conclusions reviewed. An independent cardiologist/ cardiac physiologist (accredited by the British Society of Echocardiography) will be blinded to selected echocardiograms and will validate reporting and measurements of these examinations.
Body Composition
Air-displacement plethysmography (Bodpod) is an easily accessible and safe tool to measure body composition (18). The assessment is reproducible and is comparable to other measures of body composition (18). The major advantage of Bodpod is that it is safe for patients who have had a CRT implanted. The University of Warwick and University Hospital Coventry and Warwickshire (UHCW) has one of the few facilities in their Human Metabolic Unit to perform Bodpod.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chronic Heart Failure Patients | – | Device: Cardiac Resynchronisation TherapyUndergoing CRT implantation, all will be observed for 6 months and will be defined at the end of the observation period as responder or non-responder |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Chronic heart failure patients who have been referred for and meet national criteria for Cardiac Resynchronization Therapy implants
Key inclusion criteria (8 listed)
- Age > 18 years
- Left ventricular ejection fraction ≤35% on echocardiography
- NYHA Class III/IV symptoms or milder symptoms with:
- Optimal medical therapy for heart failure that the patient tolerates (ACEi, Beta-Blocker, Mineralocorticoid) for > 3 months
- QRS duration ≥120-149msec with LBBB on resting ECG or QRS duration >150msec on resting ECG
Key exclusion criteria (8 listed)
- Acute heart failure decompensation < 6/52 before implant
- Significant cognitive impairment
- Acute coronary syndrome < 6/52 before implant
- Chronic kidney disease stage V (requiring dialysis)
- Terminal illness with likely survival < 1 year after implant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cardiac Resynchronisation TherapyRoutine implantation of CRT - part of standard of care | Device | Chronic Heart Failure Patients |
Primary outcome
Clinical Response
Time frame: 6 months
Two of three criteria must be fulfilled to be defined as a clinical response: 1. New York Heart Association (NYHA) > 1 class reduction from baseline 2. Minnesota Living with Heart Failure Questionnaire (MLHFQ) score < 5 from baseline 3. Six minute walk test (6MWT) increase in baseline distance by 10% Mortality or heart transplantation within 6 months of implant will be defined as a non-response.
2 secondary outcomes
Major Adverse Cardiovascular Outcomes
Time frame: 12 months
Echocardiographic Response
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2016.
- Background: PubMed 15753115Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L; Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005 Apr 14;352(15):1539-49. doi: 10.1056/NEJMoa050496. Epub 2005 Mar 7.
- Background: PubMed 15152059Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM; Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004 May 20;350(21):2140-50. doi: 10.1056/NEJMoa032423.
- Background: PubMed 16750706Garcia-Bolao I, Macias A, Lopez B, Gonzalez A, Gavira JJ, Azcarate P, Alegria E, Diez J. A biomarker of myocardial fibrosis predicts long-term response to cardiac resynchronization therapy. J Am Coll Cardiol. 2006 Jun 6;47(11):2335-7. doi: 10.1016/j.jacc.2006.03.012. Epub 2006 May 16. No abstract available.
- Background: PubMed 18334474Garcia-Bolao I, Lopez B, Macias A, Gavira JJ, Azcarate P, Diez J. Impact of collagen type I turnover on the long-term response to cardiac resynchronization therapy. Eur Heart J. 2008 Apr;29(7):898-906. doi: 10.1093/eurheartj/ehn098. Epub 2008 Mar 10.
- Background: PubMed 17728181Hessel MH, Bleeker GB, Bax JJ, Henneman MM, den Adel B, Klok M, Schalij MJ, Atsma DE, van der Laarse A. Reverse ventricular remodelling after cardiac resynchronization therapy is associated with a reduction in serum tenascin-C and plasma matrix metalloproteinase-9 levels. Eur J Heart Fail. 2007 Oct;9(10):1058-63. doi: 10.1016/j.ejheart.2007.07.007. Epub 2007 Aug 28.
- Background: PubMed 18768351Umar S, Bax JJ, Klok M, van Bommel RJ, Hessel MH, den Adel B, Bleeker GB, Henneman MM, Atsma DE, van der Wall EE, Schalij MJ, van der Laarse A. Myocardial collagen metabolism in failing hearts before and during cardiac resynchronization therapy. Eur J Heart Fail. 2008 Sep;10(9):878-83. doi: 10.1016/j.ejheart.2008.06.019. Epub 2008 Sep 2.
- Background: PubMed 19666898Foley PW, Stegemann B, Ng K, Ramachandran S, Proudler A, Frenneaux MP, Ng LL, Leyva F. Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy. Eur Heart J. 2009 Nov;30(22):2749-57. doi: 10.1093/eurheartj/ehp300. Epub 2009 Aug 7.
- Background: PubMed 16705077Lewandowski KC, Komorowski J, Mikhalidis DP, Bienkiewicz M, Tan BK, O'Callaghan CJ, Lewinski A, Prelevic G, Randeva HS. Effects of hormone replacement therapy type and route of administration on plasma matrix metalloproteinases and their tissue inhibitors in postmenopausal women. J Clin Endocrinol Metab. 2006 Aug;91(8):3123-30. doi: 10.1210/jc.2005-2789. Epub 2006 May 16.
- Background: PubMed 15123527Randeva HS, Lewandowski KC, Komorowski J, Murray RD, O'Callaghan CJ, Hillhouse EW, Stepien H, Shalet SM. Growth hormone replacement decreases plasma levels of matrix metalloproteinases (2 and 9) and vascular endothelial growth factor in growth hormone-deficient individuals. Circulation. 2004 May 25;109(20):2405-10. doi: 10.1161/01.CIR.0000129763.51060.77. Epub 2004 May 3.
- Background: PubMed 20651284Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010 Sep 17;107(6):810-7. doi: 10.1161/CIRCRESAHA.110.226357. Epub 2010 Jul 22.
- Background: PubMed 23283721Willeit P, Zampetaki A, Dudek K, Kaudewitz D, King A, Kirkby NS, Crosby-Nwaobi R, Prokopi M, Drozdov I, Langley SR, Sivaprasad S, Markus HS, Mitchell JA, Warner TD, Kiechl S, Mayr M. Circulating microRNAs as novel biomarkers for platelet activation. Circ Res. 2013 Feb 15;112(4):595-600. doi: 10.1161/CIRCRESAHA.111.300539. Epub 2013 Jan 2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Faizel Osman, MD FRCP FESC principal investigator
University Hospital Coventry and Warwickshire
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Heart Failure, run by University Hospitals Coventry and Warwickshire NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Response (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02541773, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2016.