Multiple Intervention and AUdit in Renal Diseases to Optimize Care
Condition: Renal Insufficiency
MeSH terms: Renal Insufficiency
Study type: Interventional
Phase: Phase 4

Summary: 
      Test whether the intensive intervention improves renal and cardiovascular outcomes in
      patients with chronic renal insufficiency.

      Test whether a multi-method intensive intervention including clinical Audit improves
      adherence to a series of quality indicators relevant to hypertension control, proteinuria,
      treatment of dyslipidemia, anemia, calcium and phosphate alterations in patients with chronic
      renal insufficiency.
    

Detailed description: 
      Background:

      Guidelines are currently promoted as a means for linking evidence based medicine to clinical
      practice and for reducing variation in clinical practice (1). However, there is ample
      evidence that implementation of evidence-based recommendations for prevention and management
      of renal disease progression and associated cardiovascular complications remain largely
      unsatisfactory (2). Deficiencies exist in the treatment of dyslipidemia and hypertension,
      inadequate use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers
      as well as in the treatment of anemia and of alterations in calcium and phosphate metabolism
      (2). Furthermore patients with diabetes mellitus infrequently receive recommended treatment
      for elevated glycosylated haemoglobin levels, hypertension, and dyslipidemia.

      The importance of interventions to increase adherence to practice guidelines and to improve
      disease control is now widely perceived. However, little is known about the relative
      effectiveness of different implementation strategies. Fresh research is required to develop
      and validate practical strategies for improving the provision of evidence-based medicine in
      nephrology clinics. In particular, studies addressing multiple common, chronic conditions
      which simultaneously affect the population of patients with chronic renal insufficiency are
      now felt as of primary importance. The study was approved by Ethical Committees of all
      Nephrology Units participating into the MAURO study.

      Specific hypotheses:

      This study is designed as a clinical trial aimed at assessing whether a quality improvement
      intervention is more effective than standard care for improving adherence to a series of
      quality indicators relevant to the prevention of renal disease progression and associated
      cardiovascular complications. The multi-method quality improvement intervention (intensive
      intervention) adds telephone and e-mail contacts (for quality improvement facilitation) and
      audits to the approach of periodic guideline dissemination used in standard care.

      Objective(s):

      Test whether the intensive intervention improves renal and cardiovascular outcomes in
      patients with chronic renal insufficiency.

      Test whether the intensive intervention improves adherence to a series of quality indicators
      relevant to hypertension control, proteinuria, treatment of dyslipidemia, anemia and calcium
      and phosphate alterations.

      Endpoints:

      The primary end point is a composite renal and cardiovascular end point, i.e. >30% decrease
      in the GFR, dialysis, transplantation, death or cardiovascular event [ECG documented angina
      or myocardial infarction, heart failure, arrhythmia (atrial fibrillation), cerebro-vascular
      event (stroke or transient ischemic attacks) or peripheral vascular diseases].

      The renal unit-level outcome is the percentage of performance targets achieved. The patient
      level outcome is the percentage of patients for whom the recommended process measures occurs.

      Key Inclusion Criteria:

        -  Average of at least 2 measurements of creatinine >1.5-4.0 mg/dL (males) and >1.3-3.5
           mg/dL (females) during the six months run-in period or albuminuria> 30 mg/24h in at
           least two consecutive visits

        -  Previous diagnosis of specific nephropathy

        -  Non acute or rapidly evolving renal diseases

        -  Age range :18 - 75 years.

        -  Non-transplanted.

        -  Non-pregnant.

        -  Not affected by cancer or diseases in the terminal phase.

      Study Design and procedures:

      Randomized, controlled clinical trial, with the renal clinic as the unit of randomization.The
      two study arms (multi-intervention including AUDIT vs standard care) will be informed on the
      general aim of the study but will be kept blinded to the type of intervention made
      [(PRospective Blinded Intervention Design (PROBID)].

      Drug Dosage, schedule and Route of Administration:

      Drugs for the treatment of blood pressure, dyslipidemia, anemia and alterations in calcium
      phosphate metabolism will be administered according to doses recommended by the guidelines
      promoted by the Italian society of Nephrology and by the KDOQI guidelines.

      Study duration:

      Three years.

      Sample Size for the primary end-point:

      The sample size was calculated with the underlying assumption that the intracluster
      correlation coefficient (ICC)(estimated in a pilot study) be 0.016. The expected annual rate
      of the primary end point (at least 36% in 3 years) was derived from a previous study (3).
      With this background in mind, we found that allocating 330 patients in the active arm and 330
      in the control arm, the study will have a 80% power for capturing as statistically
      significant (P <0.05, two tailed) a 1/3 risk reduction in three years (36% vs 24%) in the
      intensive intervention group.

      Corollary information:

      During the study a sera and DNA data-bank will be created to allow testing a series of open
      questions on renal disease progression and associated cardiovascular complications.

      Ethical considerations:

      The protocol is in conformity with the declaration of Helsinki and informed consent will be
      asked for to all participants.

      Nephrology Units participating into the MAURO study:

      Reggio Calabria, Melito(RC), Locri(RC), Palmi(RC), Taurianova(RC), Catanzaro(2 Units),
      Soverato(CZ), Lamezia(CZ), Cosenza, Lungro(CS), Rossano(CS), S.Giovanni in Fiore(CS),
      Paola(CS), Amantea-Praia a Mare(CS), Vibo Valentia-Tropea-Soriano(VV), Crotone, Messina,
      Catania, Acireale(CT), Sassari, Francavilla(TA).

      References:

        1. Hayward RS. Clinical practice guidelines on trial. CMAJ 1997; 156:1725-1727.

        2. De Nicola L, Minutolo R, Chiodini P, Zoccali C, Castellino P, Donadio C, Strippoli M,
           Casino F, Giannattasio M, Petrarulo F, Virgilio M, Laraia E, Di Iorio BR, Savica V,
           Conte G; TArget Blood Pressure LEvels in Chronic Kidney Disease (TABLE in CKD) Study
           Group. Global approach to cardiovascular risk in chronic kidney disease: reality and
           opportunities for intervention. Kidney Int 2006;69:538-545.

        3. Sarnak MJ, Greene T, Wang X, Beck G, Kusek JW, Collins AJ, Levey AS.The effect of a
           lower target blood pressure on the progression of kidney disease: long-term follow-up of
           the modification of diet in renal disease study.1: Ann Intern Med 2005; 142: 342-351.
    

Intervention name(s): Audit-driven intervention
Intervention type(s): Behavioral
Intervention description(s): Patients included in this arm will undergo to the multi-method quality improvement intervention (intensive intervention) that adds practice visits, telephone and e-mail contacts (for quality improvement facilitation) and audits to the approach of periodic guideline dissemination and feedback on demand used in the less intensive intervention.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Care Provider)
Primary purpose: Treatment
Keywords: AUDIT; Chronic kidney disease; Clinical trial; Creatinine; Multiple intervents; Nephrology guidelines.