Clinical trial NCT00400582: A Pharmacogenomic Study of Candesartan in Heart Failure
Official title: Effect of ACE Inhibitor Plus High Dose Candesartan on BNP and Inflammation in Patients With LV Dysfunction: Impact of Renin-angiotensin-aldosterone System Genetic Polymorphisms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Keywords: Heart failure
Gene polymorphism
Candesartan
ACE inhibitors
BNP
Pharmacogenomics
Lead sponsor: Montreal Heart Institute
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2006-11-17
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the impact of genetic variations on the response to candesartan in patients with heart failure who are already treated with an ACE inhibitor.


Eligibility criteria: Principal Inclusion Criteria:

1. Male or female \> or = 18 years old.
2. Symptomatic CHF corresponding to NYHA class II-IV symptoms for at least 4 weeks prior randomization.
3. LVEF \< or = 40%
4. Treatment with an optimal and stable dose of ACE inhibitor for at least 4 weeks prior to enrolment in the study.

Principal Exclusion Criteria:

1. Treatment with an ARB within 8 weeks prior to randomization.
2. Known hypersensitivity to ARBs or ACE inhibitors.
3. Creatinine clearance \< 30 ml/min or serum creatinine \> 221
4. Current serum potassium \> or = 5.0 mmol/L or a history of marked ACE inhibitor or ARB induced hyperkalemia.
5. Known bilateral renal artery stenosis.
6. Current symptomatic hypotension and/or systolic B.P. \< 90 mmHg.
7. Decompensated heart failure described as hospitalization or I.V. administration of medication in emergency room or heart failure clinic within 4 weeks
8. Stroke, acute coronary syndrome, PCI within the last 4 weeks before randomization.
9. Connective tissue disease or chronic inflammatory condition
10. Acute inflammatory process such as an infection or gout attack in the last 2 weeks.
11. Pregnant or lactating women or women of childbearing potential who are not protected from pregnancy by an accepted method of contraception.

Primary outcomes:
measure: BNP and NT-proBNP
timeFrame: 16 weeks
Secondary outcomes:
measure: Blood pressure
timeFrame: 16 weeks
measure: CRP
timeFrame: 16 weeks
measure: Renin
timeFrame: 16 weeks
measure: Aldosterone
timeFrame: 16 weeks
measure: Insulin resistance/ glucose
timeFrame: 16 weeks
measure: NYHA functional class
timeFrame: 16 weeks
measure: Tolerability
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
Study officials:
affiliation: Montreal Heart Institute
name: Michel White, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montreal Heart Institute/ Faculty of Pharmacy, University of Montreal
name: Simon de Denus, B. Pharm, MSc,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Denus S, Dube MP, Fouodjio R, Huynh T, LeBlanc MH, Lepage S, Sheppard R, Giannetti N, Lavoie J, Mansour A, Provost S, Normand V, Mongrain I, Langlois M, O'Meara E, Ducharme A, Racine N, Guertin MC, Turgeon J, Phillips MS, Rouleau JL, Tardif JC, White M; CANDIID II investigators. A prospective study of the impact of AGTR1 A1166C on the effects of candesartan in patients with heart failure. Pharmacogenomics. 2018 May;19(7):599-612. doi: 10.2217/pgs-2018-0004. Epub 2018 Apr 27.