The effects of N-acetyl cysteine (NAC) in patients with heart failure
| ISRCTN | ISRCTN66348022 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN66348022 |
| Secondary identifying numbers | N0084144632 |
- Submission date
- 30/09/2005
- Registration date
- 30/09/2005
- Last edited
- 11/07/2016
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Jonathan D Windram
Scientific
Scientific
Academic Cardiology Department
Houghton Building
Hull Royal Infirmary
Hull
HU3 2JZ
United Kingdom
| Phone | +44 (0)1482 675822 |
|---|---|
| jonwindram@hotmail.com |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | The effects of N-acetyl cysteine (NAC) in patients with heart failure: a double-blind, placebo-controlled, randomised cross-over trial |
| Study objectives | The principle aim of the study is to determine whether the drug N-acetyl cysteine (NAC) is of benefit in patients with known heart failure. Specifically we will be looking for an improvement in the ejection fraction of the left ventricle which is a measure of the heart's ability to contract. |
| Ethics approval(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | Heart failure |
| Intervention | We intend to conduct a double blind, placebo-controlled, randomised, cross-over trial comparing NAC (600 mg once daily [od], effervescent tablet Flumicil®) to placebo in patients with persistent major left ventricular systolic dysfunction and symptomatic heart failure despite maximal conventional therapy for heart failure. There will be a two-week run in phase followed by two treatment periods each lasting 12-weeks with a 4-week wash out period between phases. The cross-over design framework is one that we routinely use within our department. Patients will be selected from our outpatient heart care clinics and will be asked to participate in the trial after a full explanation of the medication to be used and the measurements involved in the trial. Prior to the run-in phase, patients' symptoms and functional capacity will be assessed using standard departmental symptom and Minnesota quality of life questionnaires, a six minute corridor walk test and a treadmill 'ramp' exercise test with metabolic gas exchange. Peripheral vascular function will be assessed using pulse wave velocity analysis (Vingmed 5 ultrasound machine, Sony, with a GE NFLA 10 megaHertz MedVascular probe) before and after nitrolingual spray. Blood will be taken to assess standard haematology and biochemistry variables including, N terminal pro-BNP, TNF, IL-6, sTNFR1, sTNFR2. Oxidative stress will be assessed by the measurement of 8-iso PGF2. The effects on the myocardial interstitium will be assessed by measuring 3 degradation markers total membrane metalloproteinase 1 (MMP-1), total tissue inhibitor of metalloproteinase 1 (TIMP 1), and the MMP-1/ TIMP 1 complex. As well as 3 extra-cellular matrix serum markers pro-collagen type I carboxy-terminal peptide (P-I-CP), pro-collagen type I amino terminal peptide (P-I-NP), and pro-collagen type III amino terminal peptide (P-III-NP). At the end of run-in, prior to randomisation, these tests will be repeated but instead of echocardiography, the patients will undergo cardiac cine-magnetic resonance imaging before and after injection of gadolinium with acquisition of late enhancement images. This will allow the myocardial substrate to be characterized as normal, scar or 'viable- but-with-reduced-contraction' using a 16 segment model. The relationship between myocardial substrate and treatment intervention will be analysed on a global and segmental basis. Baseline assessments will be repeated after 12-weeks, at the end of the washout phase (16 weeks) and at the end of study (28 weeks). Though patients have not been directly involved in the design of the trial we have in our department a long record of patient education with regard to their condition and many of our patients are very keen to undertake such studies when the benefits and possible risks are discussed in a frank and honest manner. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | N-acetyl cysteine (Flumicil®) |
| Primary outcome measure | Improvement in left ventricular ejection fraction (LVEF), measured by cine-magnetic resonance imaging. |
| Secondary outcome measures | 1. Symptoms 2. Exercise capacity 3. Natriuretic peptides 4. Serum creatinine 5. Vascular function |
| Overall study start date | 01/04/2004 |
| Completion date | 01/04/2006 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Not Specified |
| Sex | Not Specified |
| Target number of participants | 50 |
| Key inclusion criteria | Blood samples will be taken to measure N-terminal pro-brain natriuretic peptide (NT-proBNP), tumour necrotising factor (TNF), interleukin-6 (IL-6), soluble tumour necrosis factor receptor 1 (sTNFR1), soluble tumour necrosis factor receptor 2 (sTNFR2). Oxidative stress will be assessed by the measurement of 8-epimer of Prostaglandin F2 (8-iso-PGF2). The effects on the myocardial interstitium will be assessed by measuring 3 degradation markers total membrane metalloproteinase 1 (MMP-1), total tissue inhibitor of metalloproteinase 1 (TIMP 1), and the MMP-1/TIMP 1 complex. As well as 3 extra-cellular matrix serum markers pro-collagen type I carboxy-terminal peptide (P-I-CP), pro-collagen type I amino terminal peptide (P-I-NP), and pro-collagen type III amino terminal peptide (P-III-NP). They will be collected by Dr Windram and members of the nursing staff of the Department of Academic Cardiology Department. |
| Key exclusion criteria | 1. Asthma 2. Known intolerance to NAC 3. Serum creatinine greater than 200 mol/L |
| Date of first enrolment | 01/04/2004 |
| Date of final enrolment | 01/04/2006 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Hull Royal Infirmary
Hull
HU3 2JZ
United Kingdom
HU3 2JZ
United Kingdom
Sponsor information
Department of Health
Government
Government
Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
| Phone | +44 (0)20 7307 2622 |
|---|---|
| dhmail@doh.gsi.org.uk | |
| Website | http://www.dh.gov.uk/Home/fs/en |
Funders
Funder type
Government
The North and South Bank Research and Development Consortium (UK)
No information available
NHS R&D Support Funding (UK)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Editorial Notes
11/07/2016: No publications found, verifying study status with principal investigator.
