DETAIL Study: Diabetes Exposed to Telmisartan and Enalapril

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00274118
• Collaborator: (none)
• Enrollment: 250
• Locations: 37
• Duration (Months): 78
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To compare the renal consequences of two different approaches to blocking the renin angiotensin system in subjects with hypertension and concurrent Type II diabetes mellitus and diabetic nephropathy.

Condition or Disease	Intervention/Treatment	Phase
Hypertension; Diabetes Mellitus, Type 2	Drug: telmisartan; Drug: enalapril	Phase 3

Detailed Description

The aims of this study were to compare the renal consequences of two different approaches to blocking the activity of the renin angiotensin system - Angiotensin II antagonism with telmisartan and ACE inhibition with enalapril - in patients with hypertension and concurrent type II diabetes mellitus and diabetic nephropathy.

The study was designed to investigate albumin excretion rates in the short term, and in the longer term, to assess the outcome with respect to maintenance of renal function (GFR) and incidence of clinical endpoints.

Study Hypothesis:

Association of Hypertension and Diabetes Essential hypertension accounts for the majority of hypertension in people with diabetes, particularly in those with type II diabetes, who constitute more than 90% of those with a dual diagnosis of diabetes and hypertension.

Both diabetes and hypertension each confer increased cardiovascular risk, and patients with both conditions have more atherogenic risk factors.

Albumin Excretion as a Therapeutic Marker Microalbuminuria is an early and reliable predictor of diabetic nephropathy in both type I - insulin dependent diabetes mellitus (IDDM) and type II - non insulin dependent diabetes mellitus (NIDDM) patients, nephropathy being characterised by hypertension and an inevitable decline in renal function.

Furthermore, diabetic nephropathy is the single most important cause of end stage renal failure (ESRF) in the western world and over recent years the incidence of ESRF in patients with type II diabetes has dramatically increased.

In addition to predicting nephropathy, in type II diabetes, microalbuminuria also predicts mortality, the major causes of death being related to cardiovascular disease.

Comparison(s):

Selection of an ACE Inhibitor as the Comparative Agent Findings in preclinical studies of animals with diabetes mellitus suggest that ACE inhibitors reduce glomerular damage by one or more mechanisms independent of their antihypertensive effects. Glomerular efferent arteriolar tone is increased in diabetic animals and as a result there is an increase in transcapillary hydraulic pressure. These alterations may decrease the functional integrity of the glomerular capillary wall. In rats with diabetes, the long term administration of an ACE inhibitor diminishes the functional and morphologic evidence of glomerular injury and decreases glomerular transcapillary pressure. Removal of the tonic constrictor effect of angiotensin II on efferent arterioles would be expected to lower glomerular intracapillary pressure while preserving renal plasma flow.

Angiotensin II antagonists appear to be as effective as ACE inhibitors in delaying the progression of renal injury in animal models of diabetes.

Study Design

• Study Type: Interventional
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Prevention
• Official Title: DETAIL = Diabetics Exposed to Telmisartan And enalapIL: A Randomised, Double-blind, Parallel-group Comparison of the Renal and Antihypertensive Effects of Telmisartan and Enalapril in Subjects With Mild to Moderate Hypertension and Concurrent Type II Diabetes Mellitus and Diabetic Nephropathy
• Study Start Date: Jul 1, 1997
• Actual Primary Completion Date: Jan 1, 2004
• Study Completion Date: Jan 1, 2004

Outcome Measures

Primary Outcome Measures

1. Change from baseline in glomerular filtration rate GFR after five years of treatment. [5 years]

Secondary Outcome Measures

1. Change from baseline in GFR after one, two, three and four years of treatment [Baseline, 1,2,3 and 4 years]

2. Percentage change from baseline in urinary albumin excretion rate [up to 5 years]

3. Change from baseline in creatinine [up to 5 years]

4. Incidence of clinical endpoints (including- end-stage renal disease, myocardial infarction, cerebrovascular accident, congestive heart failure) [up to 5 years]

5. Incidence of all cause mortality [up to 5 years]

6. Changes in vital signs (DBP, SBP, pulse rate) [up to 5 years]

7. Number of patients with Adverse Events [up to 5 years]

8. Physical examination [up to 5 years]

9. Clinical laboratory parameters [up to 5 years]

10. Resting 12-lead ECG [up to 5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female subjects between the ages 35 and 80 years.

2. Current ACE inhibitor therapy for a minimum period of 3 months prior to study entry.

3. Confirmed diagnosis of type II diabetes:

• Subjects currently treated by diet or diet and oral hypoglycaemic drugs, OR

• Subjects currently treated with insulin, with a history of onset of diabetes after the age of 40 and a body weight in excess of ideal body weight at the time of diagnosis, and treated with oral agents for a minimum period of two years

1. On treatment diastolic blood pressure of < 95 mmHg.

2. Documentation of a normal renal ultrasound within previous 6 months prior to inclusion (alternate methods eg pyelography, renal isotope method was also acceptable).

3. Mean of three consecutive overnight urinary albumin excretion rates > 20 and < 1000 g/min at the end of the pre-treatment observation period. (A minimum of two of the three samples must be > 20 g/min.)

4. Glycosylated haemoglobin (HbA 1c) < 10%.

5. Serum creatinine < 140 mol/L.

6. Glomerular filtration rate (GFR) > 70 ml/min/1.73 m2.

7. Ability to provide written informed consent.

Exclusion Criteria:

1. Type I diabetes mellitus.

2. Pre-menopausal women (last menstruation < 1 year prior to start of screening period):

• Who were not surgically sterile (tubal ligation, hysterectomy) or

• Who were not practising acceptable means of birth control (and do not plan to continue using this method throughout the study). Acceptable methods of birth control include oral, implantable or injectable contraceptives.

• Who had a positive serum pregnancy test at baseline.

1. Afro-Caribbean subjects.

2. Mean seated SBP > 180 mmHg.

3. Hepatic dysfunction as defined by the following laboratory parameters: SGPT(ALT) or SGOT(AST) > 1.5 times the upper limit of normal.

4. Known causes of renal dysfunction other than diabetic nephropathy.

5. Subjects who had a solitary kidney or known renal artery stenosis.

6. NYHA functional class CHF II - IV.

7. Known drug or alcohol dependency.

8. Subjects receiving any investigational therapy within one month of providing written informed consent.

9. Known hypersensitivity to telmisartan or ACE inhibitors or to any component of the formulation.

10. Subjects with a history of suspected angioedema related to ACE inhibitor therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boehringer Ingelheim Investigational Site	Frederiksberg C		Denmark	DK-1900
2	Apopleksiafsnittet	Frederiksberg		Denmark	DK-2000
3	Lungemedicinsk Forskning	Hellerup		Denmark	DK-2900
4	Medical Dept. B0642	Hillerød		Denmark	DK-3400
5	Hvidovre Hospital	Hvidovre		Denmark	DK-2650
6	Gynækologisk/obstetrisk afd.	Kolding		Denmark	6000
7	Boehringer Ingelheim Investigational Site	Hyvinkää		Finland	05850
8	Boehringer Ingelheim Investigational Site	Jyväskylä		Finland	FIN-40100
9	Kuopion yliopistollinen sairaala, Keuhkoklinikka	Kuopio		Finland	FI-70211
10	Boehringer Ingelheim Investigational Site	Riihimäki		Finland	11100
11	Boehringer Ingelheim Investigational Site	Tampere		Finland	33520
12	Bosch Medicentrum	Den Bosch		Netherlands	5223 GV
13	Dept. of Internal Medicine	Utrecht		Netherlands	3584 CX
14	Boehringer Ingelheim Investigational Site	Arendal		Norway	N-4841
15	Boehringer Ingelheim Investigational Site	Jessheim		Norway	N-2050
16	Boehringer Ingelheim Investigational Site	Skogn		Norway	N-7620
17	Hjertelaget Research Foundation	Stavanger		Norway	N-4011
18	Medicinkliniken	Eksjö		Sweden	575 81
19	Medicinkliniken	Helsingborg		Sweden	251 87
20	Boehringer Ingelheim Investigational Site	Helsingborg		Sweden	254 67
21	Boehringer Ingelheim Investigational Site	Munkedal		Sweden	455 30
22	Boehringer Ingelheim Investigational Site	Tranås		Sweden	573 83
23	Boehringer Ingelheim Investigational Site	Uddevalla		Sweden	451 40
24	Samariterhemmets sjukhus	Uppsala		Sweden	751 25
25	Boehringer Ingelheim Investigational Site	Vetlanda		Sweden	574 28
26	Boehringer Ingelheim Investigational Site	Atherstone		United Kingdom	CV9 1EU
27	Boehringer Ingelheim Investigational Site	Barry		United Kingdom	CF62 7EB
28	Dept. of Diabetes	Birmingham		United Kingdom	B18 7QH
29	Department of Respiratory Medicine	Birmingham		United Kingdom	B9 5SS
30	Royal Bournemouth Hospital	Bournemouth		United Kingdom	BH7 7DW
31	Finance Office (Research Unit)	Newcastle-Upon-Tyne		United Kingdom	NE1 7RU
32	Northampton General Hospital	Northampton		United Kingdom	NN1 5BD
33	Boehringer Ingelheim Investigational Site	Northampton		United Kingdom	NN5 7AQ
34	Diabetes Centre,	Nuneaton,		United Kingdom	CV10 7DJ
35	Lucille Packard Children's Health Services at Stanford	Palo Alto		United Kingdom	94304-5786
36	Boehringer Ingelheim Investigational Site	Pontyclun		United Kingdom	CF72 9AA
37	Diabetes Centre	Rugby		United Kingdom	CV22 5PX

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim Study Coordinator, Boehringer Ingelheim Ltd./Bracknell

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00274118
• Other Study ID Numbers: 502.236
• First Posted: Jan 10, 2006
• Last Update Posted: Nov 1, 2013
• Last Verified: Oct 1, 2013

• Additional relevant MeSH terms: Hypertension; Diabetes Mellitus; Diabetes Mellitus, Type 2; Telmisartan; Enalapril

Study Results

No Results Posted as of Nov 1, 2013