N-Acetylcysteine in Heart Failure With Coexistent Chronic Renal Failure

Study Overview
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Brief Summary
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Treatment with n-acetylcysteine in patients with heart failure and chronic renal failure leads to improvements in vascular function and in renal function.

Detailed Description
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Ten patients will be invited to participate in the trial. After obtaining informed consent, the ten patients will be randomly assigned to one month of treatment with oral n-acetylcysteine 500mg or placebo twice daily for thirty days in addition to their regular therapy. At enrolment the patients will be educated and counselled about the trial and the intervention medication. Patients will also have a blood test (serum creatinine) that will allow the calculation of their renal function by use of the Cockroft Gault equation. Blood samples will also be frozen and stored. Patients will also undergo an ultrasound test of the function of their arm blood vessels. Both the blood test and the ultrasound test will be repeated at the completion of the thirty day trial period. Again the blood test sample will be frozen and stored. Subjects will then cross over to the other treatment arm for a further one month period, with the same testing at the end.

Official Title
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Randomised Control Pilot Trial of n-Acetylcysteine in the Treatment of Chronic Heart Failure With Coexistent Chronic Renal Failure.

Conditions
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Heart Failure, Congestive, Kidney Failure, Chronic

Intervention / Treatment
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* Drug: N-acetylcysteine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 75 years inclusive; Patients with chronic heart failure NYHA II, III and IV and LVEF<40%. Stable medications for 1 month. Not admitted to hospital in the past month. Chronic renal failure with GFR (as estimated by the Cockroft Gault equation) of >30 ml/min and <50 ml/min not on any form of dialysis. Exclusion Criteria: Age <18 and >75 years; Myocardial infarction in the preceding six months; Acute decompensation of renal function or heart failure in the last 30 days; Allergy to n-acetylcysteine or glyceryl trinitrate; Contraindications to the use of glyceryl trinitrate as per the product information lodged with the PBS (Australia); On treatment with allopurinol, vitamin C or vitamin E or other antioxidant therapy at time of randomisation (statins are acceptable); Acute decompensation of another organ system in the last 30 days; Current pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>5 patients: 28 days of n-acetylcysteine (in addition to standard therapy) and then repeat serum creatinine and vascular study then crossover to placebo for 28 days after one week washout period. | Drug: N-acetylcysteine<br>* 28 days of oral n-acetylcysteine (500mg bd)(in addition to standard therapy) and then repeat serum creatinine and vascular study then crossover to placebo for 28 days after one week washout period with tests repeated again at 4 weeks and 9 weeks.<br>* Other names: Mucomyst(R);|
| Placebo Comparator: 2<br>28 days of oral distilled water (5ml) (in addition to standard therapy) and then repeat serum creatinine and vascular study then crossover to intervention (N-acetylcysteine 500mg oral bd) for 28 days after one week washout period with tests repeated again at 4 weeks and 9 weeks. | Drug: N-acetylcysteine<br>* 28 days of oral n-acetylcysteine (500mg bd)(in addition to standard therapy) and then repeat serum creatinine and vascular study then crossover to placebo for 28 days after one week washout period with tests repeated again at 4 weeks and 9 weeks.<br>* Other names: Mucomyst(R);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular function via non invasive ultrasound measured flow mediated dilatation |  | baseline, 4 weeks and 9 weeks | 
| Estimated glomerular filtration rate calculated with Cockroft Gault equation. |  | baseline, 4 weeks, 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptoms of heart failure |  | baseline, 4 weeks, 9 weeks | 
| Death |  | baseline, 4 weeks, 9 weeks | 
| Serum BNP (brain natriuretic peptide) |  | baseline, 4 weeks, 9 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acetylcysteine, N-acetylcysteine, heart failure, renal failure