Mechanism of Masked Hypertension - Intervention

The University of Alabama at Birmingham

Status and phase: Withdrawn; Phase 3

Conditions: Masked Hypertension

Treatments: Drug: Carvedilol; Drug: Amlodipine

Study type: Interventional

Funder types: Other

Identifiers

NCT04121299

IRB-300004152

Details and patient eligibility

About

To test the hypothesis that sympatholytic antihypertensive antihypertensive therapy (αβ-blocker - carvedilol) will reduce out-of-clinic ambulatory BP to a greater extent by blocking sympathetic activity than non-sympatholytic antihypertensive medication (dihydropyridine calcium channel blocker - amlodipine) in individuals with masked hypertension.

Full description

A. Participants. Study participants with masked hypertension (MH) with controlled clinic BP (< 130/80 mmHg) and uncontrolled out-of-clinic awake ambulatory BP (ABP ≥ 130/80 mmHg) untreated with antihypertensive medications will be recruited.

B. Study design. This is a double-blinded, randomized, 2-period, 2-treatment crossover clinical trial comparing sympatholytic antihypertensive agent (αβ-blocker - carvedilol 40mg extended release once daily) with non-sympatholytic control agent (dihydropyridine calcium channel blocker - amlodipine 10mg once daily) in individuals with MH. All study participants will undergo out-of-clinic 24hr ABP with actigraphy monitoring for 24-hr, awake and asleep ABP; sympathetic activity assessment by BP and HR variability, 24-hour urinary catecholamines and metanephrines at baseline and after intervention. In order to avoid selection bias, patients will be randomized to their initial therapy. Patients and study personnel will be blinded to the treatment group in order to minimize information bias. An investigator without direct study involvement will be assigned the task of ensuring correct dispensing of the study medication, which will be prepared as matching capsules by the UAB Pharmacy - Investigational Drug Service. After 4 weeks of initial treatment, both treatment groups will undergo a 1-month washout where no study medication is given in order to prevent a carryover effect. The study medication will be taken in the morning between 6 and 9 am except for study visit days. A crossover design is chosen to minimize differences between study groups, as participants will act as their own controls. Electrolytes, kidney function and ECG will be monitored at each visit. Medication adherence will be determined at visit 2 (week 4) and visit 4 (week 12) by measuring 24-hr urinary specimens for medications and their metabolites by LC-MS/MS and by pill count and medication log.

C. Outcomes. The primary outcome is the difference in percent change in out-of-clinic mean 24-hr ABP, awake ABP and asleep ABP with carvedilol compared to amlodipine. Secondary outcomes include change in out-of-clinic sympathetic activity by BP and HR variability; and 24-hour urinary catecholamines and metanephrines.

D. Preliminary / anticipated results. We anticipate a greater reduction in out-of-clinic 24-hr, awake and asleep ABP due to blocking of sympathetic activity with carvedilol when compared to amlodipine use in individuals with MH. A statistically significant effect estimate will support our hypothesis that higher sympathetic activity contributes to MH, which can be managed by use of sympatholytic agents like carvedilol.

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Study participants with masked hypertension i.e. controlled clinic blood pressure (BP) and uncontrolled out-of-clinic awake ambulatory BP will be enrolled.

A. Inclusion criteria.

• Adults (18-75 years of age)
• Controlled clinic BP (< 130/80 mmHg) untreated with antihypertensive medications
• Uncontrolled awake ambulatory BP (≥ 130/80 mmHg) untreated with antihypertensive medications

B. Exclusion criteria.

• Hypertensive (Clinic BP ≥ 130/80 mmHg)
• Hypotensive (Clinic BP < 90/70 mmHg)
• Bradycardic (Heart rate < 60 beats/minute)
• Heart block
• Use of an antihypertensive medication within the last 3 months
• Use of an steroid containing medications within the last 3 months
• Body mass index ≥ 30 Kg/m2
• Chronic kidney disease (Estimated GFR < 60 mL/min/1.73m2)
• Primary aldosteronism
• Renal artery stenosis
• Pheochromocytoma
• Diabetes mellitus
• Pregnant women
• Breast feeding women
• Dementia and/or cognitive impairment prohibiting consent
• History of stroke within the past 6 months
• History of unstable angina within the past 6 months
• History of myocardial infarction within the past 6 months
• Allergy or intolerance to β-blockers
• Allergy or intolerance to calcium channel blockers

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups

Carvedilol 40mg Extended Release Once Daily

Experimental group

Description:

participants will be randomized to carvedilol 40 mg extended release once daily for the 1st or 2nd 4 week treatment period

Treatment:

Drug: Carvedilol

Amlodipine 10mg Once Daily

Active Comparator group

Description:

participants will be randomized to amlodipine 10 mg once daily for the 1st or 2nd 4 week treatment period

Treatment:

Drug: Amlodipine