Clinical trial NCT00320008: Intensified Multifactorial Intervention in Patients With Type 2 Diabetes and Microalbuminuria
Official title: Intensified Multifactorial Intervention in Patients With Type 2 Diabetes and Microalbuminuria
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Type 2 Diabetes
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
First posted: 2006-04-27
Enrollment: 160
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether intensified multifactorial intervention comprising both behaviour modification and polypharmacy can reduce the risk for late diabetic complications compared to standard treatment in patients with type 2 diabetes and microalbuminuria.

Detailed description: The overall description of the Steno-2 Study is stated in four protocols approved by the regulatory authorities in Denmark. The protocol identification numbers are KA 92071gm (4 years intervention ), KA-99035g (8 years intervention ), KA-99035-GS (13 years follow-up since intervention start) and H-KA-99035-GS (21 year follow-up since intervention start).

The aim of the study was to determine whether intensified multifactorial intervention comprising both behaviour modification and polypharmacy can reduce the risk for late diabetic complications compared to standard treatment in patients with type 2 diabetes and microalbuminuria. The primary end point after four years of intervention was to progression to diabetic nephropathy with other microvascular complications as secondary end points. The primary end point after eight years of intervention was a composite CVD endpoint with microvascular complications as secondary end points.

The interventional part of the study was ended in December 2001 after a total of eight years of intervention. From that time on, all patients were followed in a post-trial study. Also, during post-trial period all patients in both original treatment arms received similar treatment resembling the treatment given in the original intensive arm of the study. The aim of the post-trial follow-up was to investigate the effect of intensified multifactorial intervention on i) mortality and ii) years of life gained, respectively, with such an interventional approach.

Endpoints in the two parts of the post-trial follow-up:

Part one at 13 years since start of intervention:

Primary endpoint: Total mortality. Secondary endpoints: Cardiovascular endpoints as defined previously; Microvascular disease.

Part two at 21 years since start of intervention:

Primary endpoint: Difference in median time to 50% mortality in each of the two original treatment groups Secondary endpoints: Cardiovascular endpoints as defined previously; Recurrent cardiovascular events; Microvascular disease.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes
* Microalbuminuria

Exclusion Criteria:

* Stimulated serum C-peptide concentration less than 600 pmol/L
* Pancreatic insufficiency or diabetes secondary to pancreatitis
* Alcohol abuse
* Non-diabetic kidney disease
* Life-threatening disease with death probable within 4 years of study start

Primary outcomes:
measure: Diabetic nephropathy
timeFrame: Four years
measure: Combined cardiovascular endpoint
timeFrame: Eight years
measure: Total mortality
timeFrame: 13 years
measure: Years of life years gained
timeFrame: 21 years
Secondary outcomes:
measure: All cause mortality
timeFrame: 22 years
measure: Cardiovascular disease mortality
timeFrame: 22 years
measure: Stroke
timeFrame: 22 years
measure: Myocardial infarction
timeFrame: 22 years
measure: Coronary interventions
timeFrame: 22 years
measure: Amputations
timeFrame: 22 years
measure: Vascular surgery
timeFrame: 22 years
measure: Diabetic retinopathy
timeFrame: 22 years
measure: Diabetic nephropathy
timeFrame: 22 years
measure: Diabetic neuropathy
timeFrame: 22 years
Other outcomes:
Locations:
city: Slagelse
country: Denmark
facility: Slagelse Hospital
Study officials:
affiliation: Slagelse Hospital
name: Peter Gaede, Professor
role: STUDY_DIRECTOR
References:
citation: Gaede P, Vedel P, Parving HH, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study. Lancet. 1999 Feb 20;353(9153):617-22. doi: 10.1016/S0140-6736(98)07368-1.
citation: Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003 Jan 30;348(5):383-93. doi: 10.1056/NEJMoa021778.
citation: Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008 Feb 7;358(6):580-91. doi: 10.1056/NEJMoa0706245.
citation: Gaede J, Oellgaard J, Ibsen R, Gaede P, Nortoft E, Parving HH, Kjellberg J, Pedersen O. A cost analysis of intensified vs conventional multifactorial therapy in individuals with type 2 diabetes: a post hoc analysis of the Steno-2 study. Diabetologia. 2019 Jan;62(1):147-155. doi: 10.1007/s00125-018-4739-3. Epub 2018 Oct 6.
citation: Oellgaard J, Gaede P, Persson F, Rossing P, Parving HH, Pedersen O. Application of urinary proteomics as possible risk predictor of renal and cardiovascular complications in patients with type 2-diabetes and microalbuminuria. J Diabetes Complications. 2018 Dec;32(12):1133-1140. doi: 10.1016/j.jdiacomp.2018.09.012. Epub 2018 Sep 24.
citation: Kjaer LK, Oellgaard J, Henriksen T, Gaede P, Pedersen O, Poulsen HE. Indicator of RNA oxidation in urine for the prediction of mortality in patients with type 2 diabetes and microalbuminuria: A post-hoc analysis of the Steno-2 trial. Free Radic Biol Med. 2018 Dec;129:247-255. doi: 10.1016/j.freeradbiomed.2018.09.030. Epub 2018 Sep 21.
citation: Oellgaard J, Gaede P, Rossing P, Persson F, Parving HH, Pedersen O. Intensified multifactorial intervention in type 2 diabetics with microalbuminuria leads to long-term renal benefits. Kidney Int. 2017 Apr;91(4):982-988. doi: 10.1016/j.kint.2016.11.023. Epub 2017 Feb 7.
citation: Oellgaard J, Gaede P, Rossing P, Rorth R, Kober L, Parving HH, Pedersen O. Reduced risk of heart failure with intensified multifactorial intervention in individuals with type 2 diabetes and microalbuminuria: 21 years of follow-up in the randomised Steno-2 study. Diabetologia. 2018 Aug;61(8):1724-1733. doi: 10.1007/s00125-018-4642-y. Epub 2018 May 30.
citation: Gaede P, Oellgaard J, Carstensen B, Rossing P, Lund-Andersen H, Parving HH, Pedersen O. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia. 2016 Nov;59(11):2298-2307. doi: 10.1007/s00125-016-4065-6. Epub 2016 Aug 16.
citation: Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.
citation: Gaede P, Oellgaard J, Kruuse C, Rossing P, Parving HH, Pedersen O. Beneficial impact of intensified multifactorial intervention on risk of stroke: outcome of 21 years of follow-up in the randomised Steno-2 Study. Diabetologia. 2019 Sep;62(9):1575-1580. doi: 10.1007/s00125-019-4920-3. Epub 2019 Jun 1.
citation: Gaede P, Valentine WJ, Palmer AJ, Tucker DM, Lammert M, Parving HH, Pedersen O. Cost-effectiveness of intensified versus conventional multifactorial intervention in type 2 diabetes: results and projections from the Steno-2 study. Diabetes Care. 2008 Aug;31(8):1510-5. doi: 10.2337/dc07-2452. Epub 2008 Apr 28.