DETAIL Study: Diabetes Exposed to Telmisartan and Enalapril

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00274118
• Other study ID #: 502.236
• Status: Completed
• Phase: Phase 3
• First received: January 9, 2006
• Last updated: October 31, 2013
• Start date: July 1997
• Est. completion date: January 2004

Study information

• Verified date: October 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Ethics Committee, Sjaellandsgrade 40DK-2200 CPHFinland: Ethics Committee, 00029 HUSNetherlands: Committee Scientifical, 3584 CX UtrechtNorway: Regional Komite for Medisinsk, 0371 OsloSweden: Forskningsetikkommitteen, 58185 Linkoping
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. completion date: January 2004
• Est. primary completion date: January 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 80 Years

Eligibility

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

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

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

6. 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.)

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

8. Serum creatinine < 140 mol/L.

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

10. 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.

3. Afro-Caribbean subjects.

4. Mean seated SBP > 180 mmHg.

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

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

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

8. NYHA functional class CHF II - IV.

9. Known drug or alcohol dependency.

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

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

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Hypertension

Intervention

Drug:
• telmisartan

• enalapril

Locations

Country	Name	City	State
Denmark	Apopleksiafsnittet	Frederiksberg
Denmark	Boehringer Ingelheim Investigational Site	Frederiksberg C
Denmark	Lungemedicinsk Forskning	Hellerup
Denmark	Medical Dept. B0642	Hillerød
Denmark	Hvidovre Hospital	Hvidovre
Denmark	Gynækologisk/obstetrisk afd.	Kolding
Finland	Boehringer Ingelheim Investigational Site	Hyvinkää
Finland	Boehringer Ingelheim Investigational Site	Jyväskylä
Finland	Kuopion yliopistollinen sairaala, Keuhkoklinikka	Kuopio
Finland	Boehringer Ingelheim Investigational Site	Riihimäki
Finland	Boehringer Ingelheim Investigational Site	Tampere
Netherlands	Bosch Medicentrum	Den Bosch
Netherlands	Dept. of Internal Medicine	Utrecht
Norway	Boehringer Ingelheim Investigational Site	Arendal
Norway	Boehringer Ingelheim Investigational Site	Jessheim
Norway	Boehringer Ingelheim Investigational Site	Skogn
Norway	Hjertelaget Research Foundation	Stavanger
Sweden	Medicinkliniken	Eksjö
Sweden	Boehringer Ingelheim Investigational Site	Helsingborg
Sweden	Medicinkliniken	Helsingborg
Sweden	Boehringer Ingelheim Investigational Site	Munkedal
Sweden	Boehringer Ingelheim Investigational Site	Tranås
Sweden	Boehringer Ingelheim Investigational Site	Uddevalla
Sweden	Samariterhemmets sjukhus	Uppsala
Sweden	Boehringer Ingelheim Investigational Site	Vetlanda
United Kingdom	Boehringer Ingelheim Investigational Site	Atherstone
United Kingdom	Boehringer Ingelheim Investigational Site	Barry
United Kingdom	Department of Respiratory Medicine	Birmingham
United Kingdom	Dept. of Diabetes	Birmingham
United Kingdom	Royal Bournemouth Hospital	Bournemouth
United Kingdom	Finance Office (Research Unit)	Newcastle-Upon-Tyne
United Kingdom	Boehringer Ingelheim Investigational Site	Northampton
United Kingdom	Northampton General Hospital	Northampton
United Kingdom	Diabetes Centre,	Nuneaton,
United Kingdom	Lucille Packard Children's Health Services at Stanford	Palo Alto
United Kingdom	Boehringer Ingelheim Investigational Site	Pontyclun
United Kingdom	Diabetes Centre	Rugby

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Denmark,  Finland,  Netherlands,  Norway,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in glomerular filtration rate GFR after five years of treatment.		5 years	No
Secondary	Change from baseline in GFR after one, two, three and four years of treatment		Baseline, 1,2,3 and 4 years	No
Secondary	Percentage change from baseline in urinary albumin excretion rate		up to 5 years	No
Secondary	Change from baseline in creatinine		up to 5 years	No
Secondary	Incidence of clinical endpoints (including- end-stage renal disease, myocardial infarction, cerebrovascular accident, congestive heart failure)		up to 5 years	No
Secondary	Incidence of all cause mortality		up to 5 years	No
Secondary	Changes in vital signs (DBP, SBP, pulse rate)		up to 5 years	No
Secondary	Number of patients with Adverse Events		up to 5 years	No
Secondary	Physical examination		up to 5 years	No
Secondary	Clinical laboratory parameters		up to 5 years	No
Secondary	Resting 12-lead ECG		up to 5 years	No

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