Clinical trial NCT01062763: The Effect of Spironolactone on Blood Pressure in Type-2 Diabetics With Resistant Hypertension
Official title: South Danish Hypertension and Diabetes Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arterial Hypertension
Hypertension, Resistant to Conventional Therapy
Diabetes Mellitus
Keywords: hypertension
spironolactone
antihypertensive treatment
Type-2 diabetes
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
First posted: 2010-02-04
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to estimate the effect of spironolactone on blood pressure resistant to therapy in type-2 diabetics.

Detailed description: The primary object of the study is to estimate the effect of addition of low dose spironolactone to antihypertensive treatment with at least three antihypertensive drugs in patients with type-2 diabetes and blood pressure over 130/80 mmHg.

Secondary aims are to estimate how many of these patients have their blood pressure controlled by the addition of spironolactone, to investigate whether the addition of spironolactone affects insulin sensitivity and urinary protein secretion and to estimate the incidence of adverse effects of the aldosterone antagonist.

Eligibility criteria: Inclusion Criteria:

* Age \< 75 years
* Type-2 diabetes
* Therapy resistant hypertension (by ABPM)
* Treatment with at least 3 antihypertensives

Exclusion Criteria:

* HbA1c \> 10.0
* BP \> 180/110 mmHg
* Secondary hypertension
* Intolerance to spironolactone
* Permanent treatment with nonsteroidal antiinflammatory drugs or systemic glucocorticoids
* Total cholesterol 10 mmol/l
* New York Heart Association class III and IV
* Pregnancy or planned pregnancy
* Psychiatric disease
* Malignant disease
* Insufficient adherence

Primary outcomes:
measure: Change of of Systolic Blood Pressure
timeFrame: 4 months
measure: Change of Diastolic Blood Pressure
timeFrame: 4 months
Secondary outcomes:
measure: Adverse Effects
timeFrame: 4 months
Other outcomes:
Locations:
Study officials:
affiliation: Odense University Hospital
name: Ib A Jacobsen, DMSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Elliott HL, Elawad M, Wilkinson R, Singh SP. Persistence of antihypertensive efficacy after missed doses: comparison of amlodipine and nifedipine gastrointestinal therapeutic system. J Hypertens. 2002 Feb;20(2):333-8. doi: 10.1097/00004872-200202000-00025.
citation: Nishizaka MK, Zaman MA, Calhoun DA. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am J Hypertens. 2003 Nov;16(11 Pt 1):925-30. doi: 10.1016/s0895-7061(03)01032-x.
citation: Sharabi Y, Adler E, Shamis A, Nussinovitch N, Markovitz A, Grossman E. Efficacy of add-on aldosterone receptor blocker in uncontrolled hypertension. Am J Hypertens. 2006 Jul;19(7):750-5. doi: 10.1016/j.amjhyper.2005.11.016.
citation: Chapman N, Dobson J, Wilson S, Dahlof B, Sever PS, Wedel H, Poulter NR; Anglo-Scandinavian Cardiac Outcomes Trial Investigators. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension. 2007 Apr;49(4):839-45. doi: 10.1161/01.HYP.0000259805.18468.8c. Epub 2007 Feb 19.
citation: Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.
citation: Oxlund CS, Cangemi C, Henriksen JE, Jacobsen IA, Gram J, Schousboe K, Tarnow L, Argraves WS, Rasmussen LM. Low-dose spironolactone reduces plasma fibulin-1 levels in patients with type 2 diabetes and resistant hypertension. J Hum Hypertens. 2015 Jan;29(1):28-32. doi: 10.1038/jhh.2014.27. Epub 2014 Apr 17.