DETAIL Study: Diabetes Exposed to Telmisartan and Enalapril

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00274118
First received: January 9, 2006
Last updated: October 31, 2013
Last verified: October 2013
  Purpose

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 Intervention Phase
Hypertension
Diabetes Mellitus, Type 2
Drug: telmisartan
Drug: enalapril
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change from baseline in glomerular filtration rate GFR after five years of treatment. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in GFR after one, two, three and four years of treatment [ Time Frame: Baseline, 1,2,3 and 4 years ] [ Designated as safety issue: No ]
  • Percentage change from baseline in urinary albumin excretion rate [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • Change from baseline in creatinine [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • Incidence of clinical endpoints (including- end-stage renal disease, myocardial infarction, cerebrovascular accident, congestive heart failure) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • Incidence of all cause mortality [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • Changes in vital signs (DBP, SBP, pulse rate) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • Number of patients with Adverse Events [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • Physical examination [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • Clinical laboratory parameters [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • Resting 12-lead ECG [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: July 1997
Estimated Study Completion Date: January 2004
Primary Completion Date: January 2004 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   35 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00274118

Locations
Denmark
Apopleksiafsnittet
Frederiksberg, Denmark, DK-2000
Boehringer Ingelheim Investigational Site
Frederiksberg C, Denmark, DK-1900
Lungemedicinsk Forskning
Hellerup, Denmark, DK-2900
Medical Dept. B0642
Hillerød, Denmark, DK-3400
Hvidovre Hospital
Hvidovre, Denmark, DK-2650
Gynækologisk/obstetrisk afd.
Kolding, Denmark, 6000
Finland
Boehringer Ingelheim Investigational Site
Hyvinkää, Finland, 05850
Boehringer Ingelheim Investigational Site
Jyväskylä, Finland, FIN-40100
Kuopion yliopistollinen sairaala, Keuhkoklinikka
Kuopio, Finland, FI-70211
Boehringer Ingelheim Investigational Site
Riihimäki, Finland, 11100
Boehringer Ingelheim Investigational Site
Tampere, Finland, 33520
Netherlands
Bosch Medicentrum
Den Bosch, Netherlands, 5223 GV
Dept. of Internal Medicine
Utrecht, Netherlands, 3584 CX
Norway
Boehringer Ingelheim Investigational Site
Arendal, Norway, N-4841
Boehringer Ingelheim Investigational Site
Jessheim, Norway, N-2050
Boehringer Ingelheim Investigational Site
Skogn, Norway, N-7620
Hjertelaget Research Foundation
Stavanger, Norway, N-4011
Sweden
Medicinkliniken
Eksjö, Sweden, 575 81
Boehringer Ingelheim Investigational Site
Helsingborg, Sweden, 254 67
Medicinkliniken
Helsingborg, Sweden, 251 87
Boehringer Ingelheim Investigational Site
Munkedal, Sweden, 455 30
Boehringer Ingelheim Investigational Site
Tranås, Sweden, 573 83
Boehringer Ingelheim Investigational Site
Uddevalla, Sweden, 451 40
Samariterhemmets sjukhus
Uppsala, Sweden, 751 25
Boehringer Ingelheim Investigational Site
Vetlanda, Sweden, 574 28
United Kingdom
Boehringer Ingelheim Investigational Site
Atherstone, United Kingdom, CV9 1EU
Boehringer Ingelheim Investigational Site
Barry, United Kingdom, CF62 7EB
Dept. of Diabetes
Birmingham, United Kingdom, B18 7QH
Department of Respiratory Medicine
Birmingham, United Kingdom, B9 5SS
Royal Bournemouth Hospital
Bournemouth, United Kingdom, BH7 7DW
Finance Office (Research Unit)
Newcastle-Upon-Tyne, United Kingdom, NE1 7RU
Northampton General Hospital
Northampton, United Kingdom, NN1 5BD
Boehringer Ingelheim Investigational Site
Northampton, United Kingdom, NN5 7AQ
Diabetes Centre,
Nuneaton,, United Kingdom, CV10 7DJ
Lucille Packard Children's Health Services at Stanford
Palo Alto, United Kingdom, 94304-5786
Boehringer Ingelheim Investigational Site
Pontyclun, United Kingdom, CF72 9AA
Diabetes Centre
Rugby, United Kingdom, CV22 5PX
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Study Coordinator Boehringer Ingelheim Ltd./Bracknell
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00274118     History of Changes
Other Study ID Numbers: 502.236
Study First Received: January 9, 2006
Last Updated: October 31, 2013
Health Authority: Denmark: Ethics Committee, Sjaellandsgrade 40DK-2200 CPH
Finland: Ethics Committee, 00029 HUS
Netherlands: Committee Scientifical, 3584 CX Utrecht
Norway: Regional Komite for Medisinsk, 0371 Oslo
Sweden: Forskningsetikkommitteen, 58185 Linkoping

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypertension
Cardiovascular Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Vascular Diseases
Enalapril
Enalaprilat
Telmisartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014