DETAIL Study: Diabetes Exposed to Telmisartan and Enalapril
Information source: Boehringer Ingelheim Pharmaceuticals
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypertension; Diabetes Mellitus, Type 2
Intervention: telmisartan (Drug); enalapril (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Boehringer Ingelheim Pharmaceuticals Official(s) and/or principal investigator(s):
Boehringer Ingelheim Study Coordinator, Study Chair, Affiliation: Boehringer Ingelheim Ltd./Bracknell
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.
Clinical Details
Official title: 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 design: Prevention, Randomized, Double-Blind, Active Control, Parallel Assignment, Efficacy Study
Primary outcome: The key variable used to assess renal consequences was glomerular filtration rate (GFR). Change in this parameter after 5 years treatment provided the comparison between the two approaches of blocking the activity of the renin angiotensin system.
Secondary outcome: Additional variables used to evaluate renal consequences of these two approaches of blocking the activity of the renin angiotensin system included glomerular filtration rates at earlier on-treatment timepoints and urinary albumin excretion rates
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
Minimum age: 35 Years.
Maximum age: 80 Years.
Gender(s): Both.
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;
1. Subjects currently treated by diet or diet and oral hypoglycaemic drugs, or
2. 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):
1. who were not surgically sterile (tubal ligation, hysterectomy) or
2. 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.
3. 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.
Locations and Contacts
Hvidovre Hospital, Hvidovre DK-2650, Denmark
Apopleksiafsnittet, Frederiksberg DK-2000, Denmark
Gynækologisk/obstetrisk afd., Kolding 6000, Denmark
Medical Dept. B0642, Hillerød DK-3400, Denmark
Boehringer Ingelheim Investigational Site, Frederiksberg C DK-1900, Denmark
Lungemedicinsk Forskning, Hellerup DK-2900, Denmark
Boehringer Ingelheim Investigational Site, Hyvinkää 05850, Finland
Boehringer Ingelheim Investigational Site, Tampere 33520, Finland
Kuopion yliopistollinen sairaala, Keuhkoklinikka, Kuopio FI-70211, Finland
Boehringer Ingelheim Investigational Site, Jyväskylä FIN-40100, Finland
Boehringer Ingelheim Investigational Site, Riihimäki 11100, Finland
Bosch Medicentrum, Den Bosch 5223 GV, Netherlands
Dept. of Internal Medicine, Utrecht 3584 CX, Netherlands
Boehringer Ingelheim Investigational Site, Jessheim N-2050, Norway
Boehringer Ingelheim Investigational Site, Arendal N-4841, Norway
Hjertelaget Research Foundation, Stavanger N-4011, Norway
Boehringer Ingelheim Investigational Site, Skogn N-7620, Norway
Medicinkliniken, Eksjö 575 81, Sweden
Boehringer Ingelheim Investigational Site, Munkedal 455 30, Sweden
Medicinkliniken, Helsingborg 251 87, Sweden
Boehringer Ingelheim Investigational Site, 573 83 Tranås, Sweden
Boehringer Ingelheim Investigational Site, Helsingborg 254 67, Sweden
Boehringer Ingelheim Investigational Site, Uddevalla 451 40, Sweden
Boehringer Ingelheim Investigational Site, Vetlanda 574 28, Sweden
Samariterhemmets sjukhus, Uppsala 751 25, Sweden
Department of Respiratory Medicine, Birmingham B9 5SS, United Kingdom
Diabetes Centre, Rugby CV22 5PX, United Kingdom
Finance Office (Research Unit), Newcastle-Upon-Tyne NE1 7RU, United Kingdom
Dept. of Diabetes, Birmingham B18 7QH, United Kingdom
Lucille Packard Children's Health Services at Stanford, Palo Alto 94304-5786, United Kingdom
Boehringer Ingelheim Investigational Site, Pontyclun CF72 9AA, United Kingdom
Boehringer Ingelheim Investigational Site, Northampton NN5 7AQ, United Kingdom
Boehringer Ingelheim Investigational Site, Atherstone CV9 1EU, United Kingdom
Boehringer Ingelheim Investigational Site, Barry CF62 7EB, United Kingdom
Diabetes Centre,, Nuneaton, CV10 7DJ, United Kingdom
Royal Bournemouth Hospital, Bournemouth BH7 7DW, United Kingdom
Northampton General Hospital, Northampton NN1 5BD, United Kingdom
Additional Information
Starting date: July 1997
Ending date: January 2004
Last updated: April 2, 2008
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