Nephropathy In Type 2 Diabetes and Cardio-renal Events

Phase 4

Completed

Conditions: Diabetic Nephropathy

Interventions: Drug: SoC therapy
Drug: irbesartan
Drug: ramipril
Drug: hydrochlorothiazide
Drug: furosemide
Drug: amlodipine
Drug: atenolol
Drug: doxazosin
Drug: clonidine
Drug: insulin
Drug: simvastatin
Drug: fibrate
Drug: erythropoietin
Drug: aspirin

Registration Number: NCT00535925

Lead Sponsor: University of Campania "Luigi Vanvitelli"

Brief Summary: The NID-2 study, a multicentric study (21 centres enrolled), was planned in two phases:

Phase 1(observational study, completed in September 2005): after the identification of a type-2 diabetic population with typical Diabetic Nephropathy (DN), to study of the rate of renal and cardiovascular events during a middle term follow-up.

Phase 2(interventional study, started in October 2005): after randomization in two groups, a group (intervention group) is treated with an intensive multifactorial intervention whose aim is to reduce morbidity and mortality due to diabetic complications. The other group (control group) continues the conventional therapy . To avoid bias in the treatment in each center, the randomization was performed for centre.

Detailed Description: The same patients that completed the first phase of the NID-2 study (observation) were enrolled for the phase 2 of the study (intervention).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 850

Inclusion Criteria

type 2 diabetic patients
albumin extraction rate (AER= >30 mg/die (micro- or macro-albuminuric ranges) in at least two determinations in the last six months
diabetic retinopathy
patients followed in the outpatients clinic for at least 12 months

Exclusion Criteria

type 1 diabetic patients
<40 years old

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care (SoC) therapy	SoC therapy	Control group patients will continue their SoC therapy. During the study such patients could receive all the therapeutic modifications according to the good medical practice of the specialist.
Multifactorial Intensified therapy	simvastatin	An intensive multifactorial intervention according Scientific Guidelines is performed to achieve the goals for the following risk factors: hypertension, hyperglycaemia, lipids, anaemia. In particular, new antihypertensive drugs will be added one by one until the achievement of blood pressure target (\<130/80 mmHg).
Multifactorial Intensified therapy	fibrate	An intensive multifactorial intervention according Scientific Guidelines is performed to achieve the goals for the following risk factors: hypertension, hyperglycaemia, lipids, anaemia. In particular, new antihypertensive drugs will be added one by one until the achievement of blood pressure target (\<130/80 mmHg).
Multifactorial Intensified therapy	erythropoietin	An intensive multifactorial intervention according Scientific Guidelines is performed to achieve the goals for the following risk factors: hypertension, hyperglycaemia, lipids, anaemia. In particular, new antihypertensive drugs will be added one by one until the achievement of blood pressure target (\<130/80 mmHg).
Multifactorial Intensified therapy	insulin	An intensive multifactorial intervention according Scientific Guidelines is performed to achieve the goals for the following risk factors: hypertension, hyperglycaemia, lipids, anaemia. In particular, new antihypertensive drugs will be added one by one until the achievement of blood pressure target (\<130/80 mmHg).
Multifactorial Intensified therapy	irbesartan	An intensive multifactorial intervention according Scientific Guidelines is performed to achieve the goals for the following risk factors: hypertension, hyperglycaemia, lipids, anaemia. In particular, new antihypertensive drugs will be added one by one until the achievement of blood pressure target (\<130/80 mmHg).
Multifactorial Intensified therapy	ramipril	An intensive multifactorial intervention according Scientific Guidelines is performed to achieve the goals for the following risk factors: hypertension, hyperglycaemia, lipids, anaemia. In particular, new antihypertensive drugs will be added one by one until the achievement of blood pressure target (\<130/80 mmHg).
Multifactorial Intensified therapy	hydrochlorothiazide	An intensive multifactorial intervention according Scientific Guidelines is performed to achieve the goals for the following risk factors: hypertension, hyperglycaemia, lipids, anaemia. In particular, new antihypertensive drugs will be added one by one until the achievement of blood pressure target (\<130/80 mmHg).
Multifactorial Intensified therapy	furosemide	An intensive multifactorial intervention according Scientific Guidelines is performed to achieve the goals for the following risk factors: hypertension, hyperglycaemia, lipids, anaemia. In particular, new antihypertensive drugs will be added one by one until the achievement of blood pressure target (\<130/80 mmHg).
Multifactorial Intensified therapy	clonidine	An intensive multifactorial intervention according Scientific Guidelines is performed to achieve the goals for the following risk factors: hypertension, hyperglycaemia, lipids, anaemia. In particular, new antihypertensive drugs will be added one by one until the achievement of blood pressure target (\<130/80 mmHg).
Multifactorial Intensified therapy	doxazosin	An intensive multifactorial intervention according Scientific Guidelines is performed to achieve the goals for the following risk factors: hypertension, hyperglycaemia, lipids, anaemia. In particular, new antihypertensive drugs will be added one by one until the achievement of blood pressure target (\<130/80 mmHg).
Multifactorial Intensified therapy	atenolol	An intensive multifactorial intervention according Scientific Guidelines is performed to achieve the goals for the following risk factors: hypertension, hyperglycaemia, lipids, anaemia. In particular, new antihypertensive drugs will be added one by one until the achievement of blood pressure target (\<130/80 mmHg).
Multifactorial Intensified therapy	amlodipine	An intensive multifactorial intervention according Scientific Guidelines is performed to achieve the goals for the following risk factors: hypertension, hyperglycaemia, lipids, anaemia. In particular, new antihypertensive drugs will be added one by one until the achievement of blood pressure target (\<130/80 mmHg).
Multifactorial Intensified therapy	aspirin	An intensive multifactorial intervention according Scientific Guidelines is performed to achieve the goals for the following risk factors: hypertension, hyperglycaemia, lipids, anaemia. In particular, new antihypertensive drugs will be added one by one until the achievement of blood pressure target (\<130/80 mmHg).

Primary Outcome Measures

Name	Time	Method
"Number of Participants With Overall Fatal and Non-fatal, Major Adverse Cardiovascular Events (MACEs)"	4 years (in the case the number of events needed by sample size is not reached at the expected 4-year time frame, primary end point will be assessed after the follow-up phase)	number of MACEs in the two groups are reported. In addition, The primary endpoint was analyzed with event curves for the time-to-first event based on Kaplan-Meier analysis. Cox regression model was used to calculate hazard ratio (HR) and 95% Confidence Interval (CI). Due to the cluster randomized study design, a Cox shared-frailty model was fitted. multivariable model was adjusted for selected potential confounders: age, sex, systolic blood pressure (SBP), hemoglobin, estimated glomerular filtration rate (eGFR), albuminuria, HbA1c, total cholesterol and triglycerides (log-scaled) to reduce risk of bias.

Secondary Outcome Measures

Name	Time	Method
"Number of Participants Who Achieved of BP, HbA1c and Total, HDL and LDL Cholesterol Goals at the End of Intervention Phase"	13 years	Achievement of targets at end of intervention was performed applying generalized estimating equation (GEE) models, further adjusting for baseline values as covariate.