Clinical trial NCT00524615: Addition of Spironolactone in Patients With Resistant Arterial Hypertension
Official title: Addition of Spironolactone in Patients With Resistant Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hypertension
Keywords: resistant hypertension treatment
spironolactone
aldosterone antagonists
resistant arterial hypertension
refractory arterial hypertension
Lead sponsor: University Hospital Olomouc
Sponsor class: OTHER
Collaborators: name: Czech Society of Hypertension
name: Prostejov Hospital
name: Brno University Hospital
name: Olomouc Military Hospital
name: Gedeon Richter Ltd.
First posted: 2007-09-03
Enrollment: 160
Sex: ALL
Minimum age (years): 18
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 evaluate the efficacy of spironolactone on lowering blood pressure when added to therapy in patients with resistant arterial hypertension.

Detailed description: Arterial hypertension resistant to therapy and requiring treatment with more then three antihypertensive drugs is common. At present there are is no standard therapy for resistant hypertension based on randomised clinical trials, neither data to guide addition of further drugs to therapy. Recently some observational and retrospective trials reported good effect of spironolactone in patients with resistant hypertension, but these data were not validated by prospective randomised clinical trials.

This is a multicentric, randomised, double blind clinical trial, which will evaluate the effect of addition of 25 mg spironolactone to current medication compared to placebo. The study will enroll patients with blood pressure over 140/90 mmHg during a clinical examination, which are using at least three antihypertensive drugs, one of them being a diuretic. Average daytime systolic and diastolic blodd pressure will be evaluated by ABPM (ambulatory blood pressure monitoring).

Eligibility criteria: Inclusion Criteria:

* Patients over 18 years
* Resistant arterial hypertension: (blood pressure during clinical control exceeding 140/90 mmHg (or 130/80 mmHg in in diabetic patients or patients with renal disease with creatinine level of more than 133 μmol per liter or urinary protein excretion of more than 300 mg over a 24-hour period) despite adherence to treatment with full doses of at least three antihypertensive medications, including a diuretic

Exclusion Criteria:

* Pregnant or breastfeeding women, women in fertile age without ruled out pregnancy
* Severe hypertension over 180/110 mmHg
* Renal insufficiency with creatinine over 180 umol/l or GFR lower than 40 ml/min
* Hyperkalemia over 5,4 mmol/l, hyponatremia below 130 mmol/l
* Porphyria
* Hypersensitivity to the compounds of Verospiron (Richter Gedeon, Hungary) drug
* Patients taking any aldosterone antagonist (spironolactone, eplerenone, kanreone)

Primary outcomes:
measure: Average daytime systolic and diastolic blodd pressure evaluated by ABPM (ambulatory blood pressure monitoring)
timeFrame: before and after 2 months of treatment
Secondary outcomes:
measure: changes of serum potassium, natrium, creatinine, body weight, casual blood pressure in office, treatment response for different baseline levels of aldosterone and aldosterone/PRA ratio
timeFrame: 2 months of follow-up
Other outcomes:
Locations:
city: Olomouc
country: Czech Republic
facility: Olomouc University Hospital and Palacký University School of Medicine
Study officials:
affiliation: Internal medicine department I, Olomouc university hospital and Palacký University School of medicine
name: Jan Václavík, MD.
role: STUDY_DIRECTOR
affiliation: Internal Medicine Dept., Šternberk Hospital
name: Bořek Lačňák, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Internal medicine department II, Brno University Hospital
name: Martin Plachý, MD.
role: PRINCIPAL_INVESTIGATOR
References:
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: 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: Vaclavik J, Sedlak R, Jarkovsky J, Kocianova E, Taborsky M. Effect of spironolactone in resistant arterial hypertension: a randomized, double-blind, placebo-controlled trial (ASPIRANT-EXT). Medicine (Baltimore). 2014 Dec;93(27):e162. doi: 10.1097/MD.0000000000000162.
citation: Vaclavik J, Sedlak R, Plachy M, Navratil K, Plasek J, Husar R, Kocianova E, Taborsky M. Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT)--study protocol. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2011 Jun;155(2):143-8. doi: 10.5507/bp.155.2011.004.
citation: Vaclavik J, Sedlak R, Plachy M, Navratil K, Plasek J, Jarkovsky J, Vaclavik T, Husar R, Kocianova E, Taborsky M. Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT): a randomized, double-blind, placebo-controlled trial. Hypertension. 2011 Jun;57(6):1069-75. doi: 10.1161/HYPERTENSIONAHA.111.169961. Epub 2011 May 2.