Safety and Effectiveness of Drug up Titration by Nurses Specialized in Heart Failure (HF) Patients

Study Overview
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Brief Summary
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Introduction: Heart Failure (HF) generates multiple hospital admissions and mortality, which are reduced with the administration of Beta-Blocker (BB), Angiotensin Converting Enzyme Inhibitor (ACEI), Angiotensin II Receptor Blocker (ARB) and Mineralocorticoid Receptor Antagonist (MRA) drugs (Level of Evidence A). The effect is dose-dependent. Nevertheless, dosages are suboptimal. European Guidelines 2012 recommend close monitoring and up-titration of drugs by HF nurses. Trials are needed to evaluate their effectiveness and safety. Objective: To compare doses achieved by patients of BB, ACEI, ARB II and MRA in 4 months ( % relative to target doses) in the intervention group (HF nurse) and in the control group ( cardiologist), adverse events, Left Ventricular Ejection Fraction (LVEF), New York Heart Association (NYHA), 6 min. walking test, quality of life, Nt-proBNP, readmissions and mortality. Hypothesis: Non-inferiority. Design: Multicenter randomized controlled trial. New (de novo) HF patients with LVEF ≤ 40%, NYHA II-III, without contraindications to BB of 17 Spanish hospitals will be included. Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration. In the control group doses are decided by the cardiologist clinical support and education being provided by nurses. Variables: age, sex, education, psycho-social level, Cardio Vascular Risk Factors (CVRF), NYHA, LVEF, ischemic cardiopathy., N-terminal pro B-type natriuretic peptide (Nt-proBNP), 6min. walking test, Creatinine/Glomerular Filtration Rate (GFR), Potassium (K), haemoglobin, Blood Pressure (BP), Heart Rate (HR), mg./drug, European Heart Failure Self-Care Behaviour Scale (EHFScBS), Minnesota Living with Heart Failure questionnaire (MLHFQ), European Quality of life Scale (EQ-5D). Expected Results: If our hypothesis were confirmed, evidence would be provided on the effectiveness of this healthcare management, that could be economically evaluated in future studies. A qualitative study also will be undertaken to explore barriers and facilitators to implementation

Detailed Description
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No apply

Official Title
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Safety and Effectiveness of Drug up Titration by Nurses Specialized in Heart Failure (HF) Patients

Conditions
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Heart Failure

Intervention / Treatment
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* Other: Heart Failure (HF) nurse up-titration
* Other: Heart Failure (HF) cardiologist up-titration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with de novo heart Failure and LVEF <= 40% admitted in hospital, without contraindications for BB prescription with cardiologist up-titration prescription and without having achieved BB target dose previous discharge and signing informed consent. Exclusion Criteria: Contraindications for BB. Living in a nursing home. Life expectancy < 6 months. Unable to self-care or mental disease without caregiver. Unable to weight Without phone Unable to go to clinic visit.
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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Heart Failure (HF) cardiologist up-titration<br>Active Comparator:Cardiologist decides dosage with nursing clinical and educational support. | Other: Heart Failure (HF) cardiologist up-titration<br>* Up-titration of Beta-Blocker (BB), Angiotensin Converting Enzyme Inhibitor (ACEI), Angiotensin II Receptor Blocker (ARB) and Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure De Novo patients with Left Ventricular Ejection Fraction (LVEF)≤ 40%, following a protocol based on 2012 European Society of Cardiology (ESC) Heart Failure (HF) guidelines. Drugs are prescribed and titrated by the cardiologist.<br>|
| Experimental: HF nurse up-titration<br>Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration. | Other: Heart Failure (HF) nurse up-titration<br>* Up-titration of Beta-Blocker (BB), Angiotensin Converting Enzyme Inhibitor (ACEI), Angiotensin II Receptor Blocker (ARB) and Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure De Novo patients with Left Ventricular Ejection Fraction (LVEF)≤ 40%, following a protocol based on 2012 European Society of Cardiology (ESC) Heart Failure (HF) guidelines with cardiologist prescription and support.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BB % Relative Dose (Mean) With Regard to Target Dose | BB mean Relative dose is the mean dose of betablockers achieved 4 months after starting titration, relative to target dose ( %) , which is the target dose of european heart failure guidelines for BB. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Worsening Renal Function (From Baseline to 4th Month) | Number of participants with worsening renal function during the titration process (from baseline to 4 month) that could be associated to the titration process (Creatinine increase >50% baseline creatinine or creatinine>3mg/dl, or Estimated Glomerular Filtration<25 ml/min/1.73 m2) | 4 months | 
| Number of Participants With Potassium (K) ≥5.5 Meq/l (From Baseline to 4 Month) | Number of participants with Potassium≥ 5.5 meq/l during the titration process (from baseline to 4 month) that could be associated to this titration process | 4 months | 
| Number of Participants With Symptomatic Hypotension (From Baseline to 4 Month) | Description: Number of participants with symptomatic hypotension during the titration process (from baseline to 4 month) that could be associated to this titration process. Symptomatic hypotension defined as symptoms such as dizziness or light headedness, associated to hypotension | 4 months | 
| Number of Participants With Heart Rate (HR) < 50 Beats Per Minute (From Baseline to 4 Month) | Number of participants with Heart Rate (HR) < 50 beats per minute during the titration process (from baseline to 4 month) , which could be associated to the titration process. (with or without symptoms) | 4 months | 
| Number of Patients With Atrio Ventricular (AV) Block Due to Titration | Number of patients with AV Block during the titration process, associated to the BB titration | 4 months | 
| Number of Patients With Worsening of Heart Failure Signs and Symptoms | Number of patients with worsening of heart failure signs and symptoms during the titration process ( from baseline to 4 month) which could be associated to the titration process. | 4 months | 
| Number of Patients With Admissions Due to Titration | Number of patients with admissions due to titration ( not due to other causes) | 4 months | 
| Number of Patients: Mortality Due to Titration | Number of patients: Mortality due to titration ( not due to other causes) | 4 months | 
| Number of Paticipants With Drug Stop (Some Titration Drug Withdrawal Due to Intolerance, no Need or Change to Other Treatment) | number of paticipants with drug Stop ( withdrawal) that occur during the titration process that could be due to an adverse event. ( it can be not only due to an adverse event but because there is no need of this drug or its substitution for another kind of drug) | 4 months | 
| Change in % Left Ventricular Ejection Fraction | Change in % Left Ventricular Ejection Fraction (difference of change from baseline to 6 months between groups) Ejection fraction is a measurement of the percentage of blood leaving the heart each time it contracts. | 6 months | 
| N-terminal Pro-B Type Natriuretic Peptide Improvement (Nt-proBNP) | Nt-proBNP (N-terminal pro-B type natriuretic peptide) Improvement (Decrease) difference of change from baseline to 6 months between groups, mean (SD) | 6 months | 
| 6 Minute Walking Test | 6 minute walking test improvement ( change) meters.Improvement (difference of change from baseline to 6 months between groups Six minute walking test. Measurement of exercise capacity is an integral element in assessment of patients with cardiopulmonary disease. It provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions. The six-minute walk test (6MWT) measures the distance (meters) an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is allowed to self-pace and rest as needed as they traverse back and forth along a marked walkway. | 6 months | 
| Number of Participants n(%) in New York Heart Association Functional Classification I,II,III,IV | Number of participants class I-IV New York Heart Association (NYHA) functional classification, based on severity of symptoms and physical activity: NYHA I (better): No limitation of physical activity; NYHA II: Slight limitation of ordinary physical activity, breathlessness; NYHA III: marked limitation of physical activity. Comfortable at rest, but less than ordinary activity results in undue breathlessness, fatigue or palpitations; NYHA IV ( worse): unable to carry on any physical activity without discomfort.Symptoms at rest can be present. If any physical activity is undertaken discomfort is increased. | 6 months | 
| Quality of Life: MLWHFQ | Quality of Life, measured by Minnesota Living with Heart Failure Questionnaire. Improvement (change) from baseline to 6 months. Minnesota Living With Heart Failure Questionnaire (MLWHFQ). The content of this questionnaire was selected to be representative of the ways heart failure and treatments can affect the key physical, emotional, social and mental dimensions of quality of life of patients with heart failure. It consist of 21-items with score 0-5. Final evaluation moves from 0 (none) to 105 (very much); a lower score means better quality of life. | 6 months | 
| European Quality of Life Scale: EuroQol- 5 Dimension Index | European Quality of Life Scale: EuroQol- 5 Dimension index (Range: 1 full health-0 death). It measures health status self-reported by the patient. It has 5 domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is divided into three levels: 1 no problem; 2 some or moderate problems; 3 extreme problems. The EuroQol Research Foundation converts this information into a single summary index, by applying a formula that attaches specific country values (called weights) to each of the levels in each dimension. The index is calculated by subtracting the mentioned weights from 1, the value for full health. We measured the EuroQol-5D index improvement (change) from baseline to 6 months. More information in: EQ-5D-3L-User-Guide_version-6.0 (1).pdf | 6 months | 
| Number of Patients With Admissions Due to Heart Failure (HF) | Number of patients with hospital admissions due to Heart Failure. From Baseline to 6 months | 6 months | 
| Number of Patients With Deaths | Number of Patients with deaths due to Cardiovascular and non cardiovascular causes | 6 months | 
| ACEI % Relative Dose (Mean) With Regard to Target Dose | ACEI mean Relative dose is the mean dose of ACEI achieved 4 months after starting titration, relative to target dose (%) described in European guidelines | 4 Months | 
| ARB % Relative Dose (Mean) With Regard to Target Dose | ARB, angiotensin II receptor blockers, mean relative dose ( % to target dose). Target dose is described in European guidelines. Measured at 4 months after starting titration. | 4 months | 
| MRA % Relative Dose (Mean) With Regard to Target Dose | MRA % relative dose (mean) is the mean dose achieved 4 months after starting titration with regard to target dose (%) described in european guidelines | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Up-titration, Nursing or Nurse, Heart Failure