Diabetic NephropathyPhase 4NID-2NCT00535925
Nephropathy In Type 2 Diabetes and Cardio-renal Events
A Phase 4 study testing SoC therapy, irbesartan and ramipril in people with Diabetic Nephropathy, run by University of Campania Luigi Vanvitelli at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 70 years
- Conditions the study is for
- Diabetic Nephropathy
- What is being tested?
- SoC therapy, irbesartan and ramipril
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 850 participants
- Where
- 1 siteItaly
- Study dates
- Oct 2005to May 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- type 1 diabetic patients
- <40 years old
Trial locations and contacts
1 site in 1 country.
Italy1 site
Department of Advanced Medical and Surgical Sciences, Università della Campania "Luigi Vanvitelli", Naples, Italy
Naples, I-80131
About this study
Official title: Nephropathy in Type 2 Diabetes: Effects of an Intensive Multifactorial Intervention Trial on Cardio-renal Events.
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.
Read the 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).
- Conditions
- Diabetic Nephropathy
- Being tested
- SoC therapy, irbesartan, ramipril, hydrochlorothiazide, furosemide
- Keywords
- type 2 diabetes, nephropathy, cardiovascular (CV) events
- Medical subject headings
- Diabetic Nephropathies, Diabetes Mellitus, Type 2, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SoC therapyDrug
the patients have to be treated according the standard good medical practice by any center
irbesartanDrug
Therapy for hypertension:
- Step 1: irbesartan 300 mg/die and ramipril 10 mg/die
ramiprilDrug
Therapy for hypertension:
- Step 1: irbesartan 300 mg/die and ramipril 10 mg/die
hydrochlorothiazideDrug
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)
furosemideDrug
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)
amlodipineDrug
Therapy for hypertension
- Step 3: amlodipine up to 10 mg/die
atenololDrug
Therapy for hypertension
- Step 4: atenolol up to 100 mg/die
doxazosinDrug
Therapy for hypertension
- Step 5: doxazosin up to 4 mg/die
clonidineDrug
Therapy for hypertension
- Step 6: clonidine
insulinDrug
Therapy for Hyperglycaemia (to achieve HbA1c <7):
- insulin
simvastatinDrug
Therapy for hypercholesterolemia:
- for reducing LDL cholesterol < 100 mg/dl: simvastatin up to 80 mg/die
fibrateDrug
Therapy for hypertriglyceridemia
- for reducing triglycerides < 150 mg/dl and/or increasing HDL cholesterol > 40-50 mg/dl: a fibrate
erythropoietinDrug
Treatment of anaemia:
- erythropoietin
aspirinDrug
Antiplatelet therapy (in all patients without contraindications):
- aspirin up to 160 mg/die
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
"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.
Measured: 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"
Achievement of targets at end of intervention was performed applying generalized estimating equation (GEE) models, further adjusting for baseline values as covariate.
Measured: 13 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2007 (estimated)
- Study startOct 2005
- Primary completionDec 2011
- Study completionMay 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Diabetic NephropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 850 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Campania Luigi Vanvitelli
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ferdinando Carlo Sasso, MD, PhD, University of Campania Luigi Vanvitelli
- Investigators
- Ferdinando C Sasso, MD, PhD, Study director, Università della Campania "Luigi Vanvitelli", Naples, ItalyRoberto Minutolo, MD, MD, Principal investigator, Università della Campania "Luigi Vanvitelli", Naples, ItalyLuca De Nicola, MD, MD, Study chair, Università della Campania "Luigi Vanvitelli", Naples, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00535925
- Sponsor's protocol ID
- 246813579
- Acronym
- NID-2
- Status last verified
- Jul 2020
- First submitted
- 24 Sep 2007
- Last updated
- 3 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 16505495Minutolo 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.
PubMed 16877970Sasso 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.
PubMed 36344978Sasso 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.
PubMed 34271948Sasso 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.
PubMed 27733159
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nephropathy in Type 2 Diabetes: Effects of an Intensive Multifactorial Intervention Trial on Cardio-renal Events.
- ClinicalTrials.gov ID
- NCT00535925
- Acronym / sponsor ID
- NID-2 / 246813579
- Conditions
- Diabetic Nephropathy
- Keywords
- type 2 diabetes, nephropathy, cardiovascular (CV) events
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 850 participants (actual)
- Lead sponsor
- University of Campania Luigi VanvitelliUniversity, hospital or other
- Study start
- Oct 2005 (actual)
- Primary completion
- Dec 2011 (actual)
- Study completion
- May 2019 (actual)
- First posted
- 27 Sep 2007 (estimated)
- Results
- Posted 11 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care (SoC) therapy | Active comparator | Drug: SoC therapyControl 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 | Experimental | 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: aspirinAn 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). |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (2 listed)
- type 1 diabetic patients
- <40 years old
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SoC therapythe patients have to be treated according the standard good medical practice by any center | Drug | Standard of Care (SoC) therapy |
| irbesartanTherapy for hypertension: - Step 1: irbesartan 300 mg/die and ramipril 10 mg/die | Drug | Multifactorial Intensified therapy |
| ramiprilTherapy for hypertension: - Step 1: irbesartan 300 mg/die and ramipril 10 mg/die | Drug | Multifactorial Intensified therapy |
| hydrochlorothiazideTherapy 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 | Multifactorial Intensified therapy |
| furosemideTherapy 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 | Multifactorial Intensified therapy |
| amlodipineTherapy for hypertension - Step 3: amlodipine up to 10 mg/die | Drug | Multifactorial Intensified therapy |
| atenololTherapy for hypertension - Step 4: atenolol up to 100 mg/die | Drug | Multifactorial Intensified therapy |
| doxazosinTherapy for hypertension - Step 5: doxazosin up to 4 mg/die | Drug | Multifactorial Intensified therapy |
| clonidineTherapy for hypertension - Step 6: clonidine | Drug | Multifactorial Intensified therapy |
| insulinTherapy for Hyperglycaemia (to achieve HbA1c <7): - insulin | Drug | Multifactorial Intensified therapy |
| simvastatinTherapy for hypercholesterolemia: - for reducing LDL cholesterol < 100 mg/dl: simvastatin up to 80 mg/die | Drug | Multifactorial Intensified therapy |
| fibrateTherapy for hypertriglyceridemia - for reducing triglycerides < 150 mg/dl and/or increasing HDL cholesterol > 40-50 mg/dl: a fibrate | Drug | Multifactorial Intensified therapy |
| erythropoietinTreatment of anaemia: - erythropoietin | Drug | Multifactorial Intensified therapy |
| aspirinAntiplatelet therapy (in all patients without contraindications): - aspirin up to 160 mg/die | Drug | Multifactorial Intensified therapy |
Primary outcome
"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.
1 secondary outcome
"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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16505495Sasso 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.
- Background: PubMed 16877970Minutolo 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.
- Derived from this study: PubMed 36344978Sasso 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.
- Derived from this study: PubMed 34271948Sasso 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.
- Derived from this study: PubMed 27733159Sasso 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ferdinando C Sasso, MD, PhD study director
Università della Campania "Luigi Vanvitelli", Naples, Italy
Roberto Minutolo, MD, MD principal investigator
Università della Campania "Luigi Vanvitelli", Naples, Italy
Luca De Nicola, MD, MD study chair
Università della Campania "Luigi Vanvitelli", Naples, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing SoC therapy, irbesartan and ramipril in people with Diabetic Nephropathy, run by University of Campania Luigi Vanvitelli at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
"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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00535925, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2020.