Chronic heart failure.
Conditions
Interventions
Trade Name: Azithromycin
Product Name: Azithromycin
Product Code: N/A
Pharmaceutical Form: Tablet
INN or Proposed INN: Azithromycin
Sponsors
Hull and East Yorkshire Hospitals NHS Trust.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Ability to give, legally valid, written informed consent • Clinical diagnosis of heart failure • NT-proBNP plasma concentration >400ng/L • Procalcitonin plasma concentration >50 pg/ml Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: • Age <18 years • Inability to understand or read English. • Women of child bearing potential • Antibiotic use in the prior 6 weeks • Endocarditis • Any known cancer • Previous major adverse effect to azithromycin or metronidazole (eg:- allergy, severe diarrhoea, need for hospital treatment of adverse effect) • Unwilling to avoid alcohol for one week (requested in all arms of the study) • Surgery of any kind in previous 6 weeks (includes device implantation) • Heart transplant recipient • Recipient of a left ventricular assist device • Inability to follow instructions or comply with follow-up procedures • Porphyria (use of macrolides and metronidazole is contra indicated ) • Contra-indications to one week’s treatment with azithromycin, metronidazole (if not already listed in the exclusion criteria)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In patients with heart failure who have an elevated concentration of procalcitonin (a marker of infection) which is not explained by clinical evidence of infection, can treatment for one week with azithromycin or with metronidazole reduce plasma concentrations of procalcitonin compared to a control group who receive no antibiotics. Procalcitonin is associated with a poor prognosis so understanding the mechanism for an elevated concentration in those without infection may provide a therapeutic target.; Secondary Objective: Secondary endpoints are : Change in procalcitonin between baseline and two weeks change in procalcitonin between baseline and six weeks change in procalcitonin between one and two weeks change in procalcitonin between one and six weeks change in cardiovascular measurements at one, two and six week; time course of any cardiovascular changes and their relationship to changes in procalcitonin In addition, we will evaluate the patients’ haemodynamic profiles in detail using painless, non-invasive technologies including measure of pulse wave velocity and characteristics (ENVERDIS), bio-impedance (NICAS), photo-plethysmography (NEXFIN) and Echocardiography. We will also measure a range of cardiovascular risk markers including(NT-proBNP, Galectin-3), inflammatory (hsCRP, PCT, acylation stimulatory protein, lipopolysaccharides and renal (NGAL) biomarkers in plasma, serum or urine. ; Primary end point(s): The primary endpoint is change in procalcitonin from baseline to the evaluation at 7-days in patients who either receive an antibiotic compared to those that do not. We intend to compare a) Both antibiotic arms grouped together to no antibiotic therapy b) Azithromycin to no therapy c) Metronidazole to no therapy ;Timepoint(s) of evaluation o | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in procalcitonin between o baseline and two weeks o baseline and six weeks o one and two weeks o one and six weeks • Changes in hsCRP, NT-proBNP, serum urea and creatinine, systolic blood pressure, systemic vascular resistance, augmentation index at one, two and six weeks. • Relationships between changes in procalcitonin and changes in hsCRP, NT-proBNP, serum urea and creatinine, acyaltion stimulatory protein, lipopolysaccaharides, systolic blood pressure, systemic vascular resistance, global augmentation index at one, two and six weeks. ;Timepoint(s) of evaluation of this end point: Same as primary end-points | — |
Countries
United Kingdom
Contacts
Public ContactJames Hobkirk
University of Hull
Outcome results
None listed