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Reversal of an Unfavorable Effect of Hydrochlorothiazide Compared to Angiotensin Converting Enzyme Inhibitor on Serum Uric Acid and Oxypurines Levels by Estrogen-progestin Therapy in Hypertensive Postmenopausal Women.

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ClinicalTrials.gov Identifier: NCT03921736
Recruitment Status : Completed
First Posted : April 19, 2019
Last Update Posted : April 22, 2019
Sponsor:
Information provided by (Responsible Party):
Anna Posadzy-Małaczyńska, Poznan University of Medical Sciences

Brief Summary:
The aim was to assess the effect of estrogen-progestin therapy (EPT) on serum levels of uric acid (SUA) and its precursors: xanthine (X) and hypoxanthine (HX) and on uric acid (UA) renal excretion in hypertensive postmenopausal women treated with an angiotensin-converting enzyme inhibitor (ACEI) or thiazide diuretic (HCTZ).

Condition or disease Intervention/treatment Phase
Hypertension Hyperuricemia Menopause Drug: Perindopril Drug: Hydrochlorothiazide Drug: Estracomb TTS Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Postmenopausal women with, untreated essential hypertension were recruited to the study. The control group consisted of 40 postmenopausal women with normal blood pressure.
Masking: Single (Investigator)
Primary Purpose: Treatment
Official Title: Reversal of an Unfavorable Effect of Hydrochlorothiazide Compared to Angiotensin Converting Enzyme Inhibitor on Serum Uric Acid and Oxypurines Levels by Estrogen-progestin Therapy in Hypertensive Postmenopausal Women.
Actual Study Start Date : January 10, 2000
Actual Primary Completion Date : March 6, 2001
Actual Study Completion Date : November 17, 2005

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: Control Group
Control group consisted of 40 postmenopausal women with normal blood pressure.
Experimental: Hypertensive women group receiving hydrochlorothiazide
Patients received hydrochlorothiazide 25 mg/day p.o. for 1 year.
Drug: Hydrochlorothiazide
hydrochlorothiazide 25 mg/day p.o. for 12 months

Experimental: Hypertensive women group receiving perindopril.
Patients received perindopril 4 mg/day p.o for 1 year.
Drug: Perindopril
4 mg/day p.o. for 12 months

Experimental: Hypertensive women group receiving hydrochlorothiazide and EPT
Patients received hydrochlorothiazide 25 mg/day p.o. and estrogen-progestin therapy- transdermal patches releasing 17β-estradiol (0.05 mg/24 hours) and norethisterone (0.25 mg/24 hours) for 1 year
Drug: Hydrochlorothiazide
hydrochlorothiazide 25 mg/day p.o. for 12 months

Drug: Estracomb TTS
Transdermal patches releasing 17β-estradiol (0.05 mg/24 hours) and norethisterone (0.25 mg/24 hours) for 12 months

Experimental: Hypertensive women group receiving perindopril and EPT.
Patients received perindopril 4 mg/day p.o and estrogen-progestin therapy- transdermal patches releasing 17β-estradiol (0.05 mg/24 hours) and norethisterone (0.25 mg/24 hours) for 1 year
Drug: Perindopril
4 mg/day p.o. for 12 months

Drug: Estracomb TTS
Transdermal patches releasing 17β-estradiol (0.05 mg/24 hours) and norethisterone (0.25 mg/24 hours) for 12 months

Experimental: Hipotensive women group receiving EPT.
Patients received estrogen-progestin therapy- transdermal patches releasing 17β-estradiol (0.05 mg/24 hours) and norethisterone (0.25 mg/24 hours) for 1 year.
Drug: Estracomb TTS
Transdermal patches releasing 17β-estradiol (0.05 mg/24 hours) and norethisterone (0.25 mg/24 hours) for 12 months




Primary Outcome Measures :
  1. Blood pressure in mmHg [ Time Frame: 12 months ]

    As compared with normotensive women, hypertensive women showed higher office and ambulatory blood pressure, as well as a lower night-time decrease in systolic and diastolic blood pressure.

    Both perindopril and hydrochlorothiazide led to a similar reduction in arterial blood pressure in hypertensive women.

    After 12 months of treatment, statistically significant differences were observed between the EPT+ and EPT- subgroups in systolic and diastolic office-based blood pressure in the study group treated with ACEI. Such effect of EPT on ABPM(ambulatory blood pressure monitoring) was not observed in all study participants. Multiple linear regression models have shown that after 12 months of antihypertensive treatment there were no significant differences in night-time decrease in blood pressure caused by EPT treatment, despite its significant change when compared to baseline values for ACEI and HCTZ subgroups.



Secondary Outcome Measures :
  1. Renal plasma flow in ml/min [ Time Frame: 12 months ]

    As compared with normotensive women, hypertensive women showed lower GFR and RPF.

    Glomerular filtration rate (GFR) remained unaltered in all subgroups throughout the duration of the study. When compared to the baseline values, renal plasma flow (RPF) increased significantly in women treated with perindopril, both with and without EPT. At the end of the study, there were no differences in RPF in the two subgroups of ACEI (EPT+ vs EPT-) groups. RPF also increased in women treated with hydrochlorothiazide and receiving EPT. However, RPF was substantially reduced in the subgroup of women treated with hydrochlorothiazide without EPT.



Other Outcome Measures:
  1. Serum uric acid levels in mg/dl [ Time Frame: 12 months ]

    Hypertensive women had significantly higher serum uric acid levels than normotensive women, whereas clearance and fractional excretion of uric acid were significantly lower in hypertensive than in normotensive women.

    Uric acid levels in plasma decreased significantly in women treated with perindopril, both in the subgroup receiving and not receiving hormone replacement therapy (HRT).

    At the end of the study, there were no significant differences in plasma uric acid levels in two subgroups treated with ACEI (EPT+ vs EPT-) In hypertensive women treated with hydrochlorothiazide, uric acid concentrations in plasma decreased significantly when compared to the baseline values, but only in the subgroup receiving estrogen-progestin therapy.


  2. Serum xanthine and hypoxanthine levels in mg/dl [ Time Frame: 12 months ]

    In the groups of hypertensive women, serum xanthine and hypoxanthine levels were significantly higher than in the group of normotensive women.

    In multivariate analysis, behavior of xanthine and hypoxanthine in the subgroups treated with or without EPT showed significant differences in patients treated with diuretic. In women treated with ACEI with or without EPT, only hypoxanthine levels decreased significantly




Information from the National Library of Medicine

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Ages Eligible for Study:   49 Years to 53 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Treatment-naive postmenopausal women
  • Diagnosed hypertension (grade 1 or 2 according to ESH/ESC 2013 guidelines)

Exclusion Criteria:

  • breast cancer in a first-degree relative
  • hyperplasia diagnosed by endometrial biopsy,
  • history of thromboembolic diseases,
  • current or history of use of estrogen-progestin therapy or contraceptives
  • diabetes,
  • kidney failure,
  • thyroid disease,
  • heart and other chronic diseases (secondary hypertension, atrial fibrillation)

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Anna Posadzy-Małaczyńska, Habilitated doctor of Medical Sciences in Medicine, Poznan University of Medical Sciences
ClinicalTrials.gov Identifier: NCT03921736     History of Changes
Other Study ID Numbers: 1319/99
First Posted: April 19, 2019    Key Record Dates
Last Update Posted: April 22, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Anna Posadzy-Małaczyńska, Poznan University of Medical Sciences:
estrogen-progestin therapy
hypertension
uric acid
xanthine
hypoxanthine
menopause
thiazide diuretic
angiotensin-converting enzyme inhibitor

Additional relevant MeSH terms:
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Hypertension
Hyperuricemia
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Estradiol
Estrogens
Polyestradiol phosphate
Hydrochlorothiazide
Perindopril
Enzyme Inhibitors
Uric Acid
Angiotensin-Converting Enzyme Inhibitors
Progestins
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Norethindrone
Norethindrone Acetate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antihypertensive Agents
Diuretics
Natriuretic Agents
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antioxidants
Protective Agents
Protease Inhibitors