Condition category
Circulatory System
Date applied
30/09/2005
Date assigned
30/09/2005
Last edited
11/07/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Jonathan D Windram

ORCID ID

Contact details

Academic Cardiology Department
Houghton Building
Hull Royal Infirmary
Hull
HU3 2JZ
United Kingdom
+44 (0)1482 675822
jonwindram@hotmail.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N0084144632

Study information

Scientific title

The effects of N-acetyl cysteine (NAC) in patients with heart failure: a double-blind, placebo-controlled, randomised cross-over trial

Acronym

Study hypothesis

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

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

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

Phase

Not Applicable

Drug names

N-acetyl cysteine (Flumicil®)

Primary outcome measures

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 trial start date

01/04/2004

Overall trial end date

01/04/2006

Reason abandoned

Eligibility

Participant 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.

Participant type

Patient

Age group

Not Specified

Gender

Not Specified

Target number of participants

50

Participant exclusion criteria

1. Asthma
2. Known intolerance to NAC
3. Serum creatinine greater than 200 mol/L

Recruitment start date

01/04/2004

Recruitment end date

01/04/2006

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Hull Royal Infirmary
Hull
HU3 2JZ
United Kingdom

Sponsor information

Organisation

Department of Health

Sponsor details

Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
+44 (0)20 7307 2622
dhmail@doh.gsi.org.uk

Sponsor type

Government

Website

http://www.dh.gov.uk/Home/fs/en

Funders

Funder type

Government

Funder name

The North and South Bank Research and Development Consortium (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

NHS R&D Support Funding (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

11/07/2016: No publications found, verifying study status with principal investigator.