Nephropathy In Type 2 Diabetes and Cardio-renal Events

NCT00535925 | Completed Phase 4 Results DMC

• 1 other identifier: 246813579
• Study Type: interventional
• Target: 850
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetic Nephropathy

Keywords

type 2 diabetes; nephropathy; cardiovascular (CV) events

Outcome Measures

Primary Outcomes (1)

• "Number of Participants With Overall Fatal and Non-fatal, Major Adverse Cardiovascular Events (MACEs)"

  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.

  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)

Secondary Outcomes (1)

• "Number of Participants Who Achieved of BP, HbA1c and Total, HDL and LDL Cholesterol Goals at the End of Intervention Phase"

  13 years

Study Arms (2)

Standard of Care (SoC) therapy

ACTIVE COMPARATOR

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

Multifactorial Intensified therapy

EXPERIMENTAL

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; Drug: ramipril; Drug: hydrochlorothiazide; Drug: furosemide; Drug: amlodipine; Drug: atenolol; Drug: doxazosin; Drug: clonidine; Drug: insulin; Drug: simvastatin; Drug: fibrate; Drug: erythropoietin; Drug: aspirin

Interventions

SoC therapy DRUG

the patients have to be treated according the standard good medical practice by any center

Standard of Care (SoC) therapy

irbesartan DRUG

Therapy for hypertension: \- Step 1: irbesartan 300 mg/die and ramipril 10 mg/die

Multifactorial Intensified therapy

ramipril DRUG

Therapy for hypertension: \- Step 1: irbesartan 300 mg/die and ramipril 10 mg/die

Multifactorial Intensified therapy

hydrochlorothiazide DRUG

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)

Multifactorial Intensified therapy

furosemide DRUG

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)

Multifactorial Intensified therapy

amlodipine DRUG

Therapy for hypertension \- Step 3: amlodipine up to 10 mg/die

Multifactorial Intensified therapy

atenolol DRUG

Therapy for hypertension \- Step 4: atenolol up to 100 mg/die

Multifactorial Intensified therapy

doxazosin DRUG

Therapy for hypertension \- Step 5: doxazosin up to 4 mg/die

Multifactorial Intensified therapy

clonidine DRUG

Therapy for hypertension \- Step 6: clonidine

Multifactorial Intensified therapy

insulin DRUG

Therapy for Hyperglycaemia (to achieve HbA1c \<7): \- insulin

Multifactorial Intensified therapy

simvastatin DRUG

Therapy for hypercholesterolemia: \- for reducing LDL cholesterol \< 100 mg/dl: simvastatin up to 80 mg/die

Multifactorial Intensified therapy

fibrate DRUG

Therapy for hypertriglyceridemia \- for reducing triglycerides \< 150 mg/dl and/or increasing HDL cholesterol \> 40-50 mg/dl: a fibrate

Multifactorial Intensified therapy

erythropoietin DRUG

Treatment of anaemia: \- erythropoietin

Multifactorial Intensified therapy

aspirin DRUG

Antiplatelet therapy (in all patients without contraindications): \- aspirin up to 160 mg/die

Multifactorial Intensified therapy

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• type 1 diabetic patients
• \<40 years old

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead

Study Sites (1)

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

Naples, I-80131, Italy

Location

Related Publications (5)

• 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.

  PMID: 16505495 BACKGROUND

• 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.

  PMID: 16877970 BACKGROUND

• 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.

  PMID: 36344978 DERIVED

• 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.

  PMID: 34271948 DERIVED

• 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.

  PMID: 27733159 DERIVED

MeSH Terms

Conditions

Diabetic Nephropathies; Diabetes Mellitus, Type 2; Kidney Diseases

Interventions

Irbesartan; Ramipril; Hydrochlorothiazide; Furosemide; Amlodipine; Atenolol; Doxazosin; Clonidine; Insulin; Simvastatin; Fibric Acids; Erythropoietin; Aspirin

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Spiro Compounds; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Thiazides; Sulfanilamides; Amides; Aniline Compounds; Amines; Dihydropyridines; Pyridines; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Prazosin; Quinazolines; Imidazolines; Imidazoles; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Phenyl Ethers; Ethers; Phenols; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors; Salicylates; Hydroxybenzoates

Results Point of Contact

• Title: Prof. Ferdinando Carlo Sasso. MD, PhD
• Organization: University of Campania

ferdinandocarlo.sasso@unicampania.it

+39-081-5665010

Study Officials

• Ferdinando C Sasso, MD, PhD

  Università della Campania "Luigi Vanvitelli", Naples, Italy

  STUDY DIRECTOR

• Roberto Minutolo, MD, MD

  Università della Campania "Luigi Vanvitelli", Naples, Italy

  PRINCIPAL INVESTIGATOR

• Luca De Nicola, MD, MD

  Università della Campania "Luigi Vanvitelli", Naples, Italy

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: AssociateProfessor

Study Record Dates

• First Submitted: September 24, 2007
• First Posted: September 27, 2007
• Study Start: October 1, 2005
• Primary Completion: December 1, 2011
• Study Completion: May 1, 2019
• Last Updated: August 3, 2020
• Results First Posted: May 11, 2020

Record last verified: 2020-07

Locations

IT (1)