Nephropathy In Type 2 Diabetes and Cardio-renal Events (NID-2)

• ClinicalTrials.gov Identifier: NCT00535925
• Recruitment Status: Completed
• First Posted: September 27, 2007
• Results First Posted: May 11, 2020
• Last Update Posted: August 3, 2020
• Sponsor: University of Campania "Luigi Vanvitelli"
• Information provided by (Responsible Party): Ferdinando Carlo Sasso, MD, PhD, University of Campania "Luigi Vanvitelli"

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Diabetic Nephropathy	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	Phase 4

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 850 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Nephropathy in Type 2 Diabetes: Effects of an Intensive Multifactorial Intervention Trial on Cardio-renal Events.
• Actual Study Start Date: October 2005
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: May 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Standard of Care (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.	Drug: SoC therapy; the patients have to be treated according the standard good medical practice by any center
Experimental: Multifactorial Intensified therapy; 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).	Drug: irbesartan; Therapy for hypertension: - Step 1: irbesartan 300 mg/die and ramipril 10 mg/die; Drug: ramipril; Therapy for hypertension: - Step 1: irbesartan 300 mg/die and ramipril 10 mg/die; Drug: hydrochlorothiazide; Therapy for hypertension - Step 2: Diuretic (hydrochlorothiazide 12.5-25 mg/die if serum creatinine <2 mg/dl, furosemide 25-75 mg/die if serum creatinin ≥2 mg/dl); Drug: furosemide; Therapy for hypertension - Step 2: Diuretic (hydrochlorothiazide 12.5-25 mg/die if serum creatinine <2 mg/dl, furosemide 25-75 mg/die if serum creatinin ≥2 mg/dl); Drug: amlodipine; Therapy for hypertension - Step 3: amlodipine up to 10 mg/die; Drug: atenolol; Therapy for hypertension - Step 4: atenolol up to 100 mg/die; Drug: doxazosin; Therapy for hypertension - Step 5: doxazosin up to 4 mg/die; Drug: clonidine; Therapy for hypertension - Step 6: clonidine; Drug: insulin; Therapy for Hyperglycaemia (to achieve HbA1c <7): - insulin; Drug: simvastatin; Therapy for hypercholesterolemia: - for reducing LDL cholesterol < 100 mg/dl: simvastatin up to 80 mg/die; Drug: fibrate; Therapy for hypertriglyceridemia - for reducing triglycerides < 150 mg/dl and/or increasing HDL cholesterol > 40-50 mg/dl: a fibrate; Drug: erythropoietin; Treatment of anaemia: - erythropoietin; Drug: aspirin; Antiplatelet therapy (in all patients without contraindications): - aspirin up to 160 mg/die

Outcome Measures

Primary Outcome Measures :

1. "Number of Participants With Overall Fatal and Non-fatal, Major Adverse Cardiovascular Events (MACEs)" [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Italy

Department of Advanced Medical and Surgical Sciences, Università della Campania "Luigi Vanvitelli", Naples, Italy

Naples, Italy, I-80131

Sponsors and Collaborators

University of Campania "Luigi Vanvitelli"

Investigators

• Study Director: Ferdinando C Sasso, MD, PhD; Università della Campania "Luigi Vanvitelli", Naples, Italy
• Principal Investigator: Roberto Minutolo, MD, MD; Università della Campania "Luigi Vanvitelli", Naples, Italy
• Study Chair: Luca De Nicola, MD, MD; Università della Campania "Luigi Vanvitelli", Naples, Italy

More Information

Publications:

Sasso FC, De Nicola L, Carbonara O, Nasti R, Minutolo R, Salvatore T, Conte G, Torella R. Cardiovascular risk factors and disease management in type 2 diabetic patients with diabetic nephropathy. Diabetes Care. 2006 Mar;29(3):498-503. doi: 10.2337/diacare.29.03.06.dc05-1776.

Minutolo R, Sasso FC, Chiodini P, Cianciaruso B, Carbonara O, Zamboli P, Tirino G, Pota A, Torella R, Conte G, De Nicola L. Management of cardiovascular risk factors in advanced type 2 diabetic nephropathy: a comparative analysis in nephrology, diabetology and primary care settings. J Hypertens. 2006 Aug;24(8):1655-61. doi: 10.1097/01.hjh.0000239303.93872.31.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sasso FC, Simeon V, Galiero R, Caturano A, De Nicola L, Chiodini P, Rinaldi L, Salvatore T, Lettieri M, Nevola R, Sardu C, Docimo G, Loffredo G, Marfella R, Adinolfi LE, Minutolo R; NID-2 study group Investigators. The number of risk factors not at target is associated with cardiovascular risk in a type 2 diabetic population with albuminuria in primary cardiovascular prevention. Post-hoc analysis of the NID-2 trial. Cardiovasc Diabetol. 2022 Nov 7;21(1):235. doi: 10.1186/s12933-022-01674-7.

Sasso FC, Pafundi PC, Simeon V, De Nicola L, Chiodini P, Galiero R, Rinaldi L, Nevola R, Salvatore T, Sardu C, Marfella R, Adinolfi LE, Minutolo R; NID-2 Study Group Investigators. Efficacy and durability of multifactorial intervention on mortality and MACEs: a randomized clinical trial in type-2 diabetic kidney disease. Cardiovasc Diabetol. 2021 Jul 16;20(1):145. doi: 10.1186/s12933-021-01343-1.

Sasso FC, Lascar N, Ascione A, Carbonara O, De Nicola L, Minutolo R, Salvatore T, Rizzo MR, Cirillo P, Paolisso G, Marfella R; NID-2 study group. Moderate-intensity statin therapy seems ineffective in primary cardiovascular prevention in patients with type 2 diabetes complicated by nephropathy. A multicenter prospective 8 years follow up study. Cardiovasc Diabetol. 2016 Oct 13;15(1):147. doi: 10.1186/s12933-016-0463-9.

• Responsible Party: Ferdinando Carlo Sasso, MD, PhD, AssociateProfessor, University of Campania "Luigi Vanvitelli"
• ClinicalTrials.gov Identifier: NCT00535925
• Other Study ID Numbers: 246813579
• First Posted: September 27, 2007
• Results First Posted: May 11, 2020
• Last Update Posted: August 3, 2020
• Last Verified: July 2020

Keywords provided by Ferdinando Carlo Sasso, MD, PhD, University of Campania "Luigi Vanvitelli":

type 2 diabetes; nephropathy; cardiovascular (CV) events

Additional relevant MeSH terms:

Kidney Diseases; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Urologic Diseases; Diabetes Complications; Aspirin; Atenolol; Amlodipine; Hydrochlorothiazide; Clonidine; Ramipril; Irbesartan; Doxazosin; Furosemide; Epoetin Alfa; Simvastatin; Physiological Effects of Drugs; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents