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Manidipine Versus Amlodipine in Patients With Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03106597
Recruitment Status : Terminated (Difficulty in enrolling subjects)
First Posted : April 10, 2017
Last Update Posted : September 4, 2020
Sponsor:
Collaborator:
Takeda Pharmaceuticals International, Inc.
Information provided by (Responsible Party):
Eung Ju Kim, Korea University Guro Hospital

Brief Summary:
The purpose of this study is to evaluate the effect of a third-generation Calcium Channel Blocker (CCB), manidipine, compared with second-generation Calcium Channel Blocker (CCB), amlodipine, on the development of peripheral edema using Direct Segmental Multi-Frequency Bioelectrical Impedance Analysis (DSM-BIA) method in patients with mild to moderate essential hypertension. Investigator expects this study could show more objective evidence of better safety of manidipine compared with amlodipine for peripheral edema.

Condition or disease Intervention/treatment Phase
Hypertension Drug: Manidipine 20mg Drug: Amlodipine 10mg Phase 4

Detailed Description:

Dihydropyridine Calcium Channel Blockers (CCBs) are one of the most commonly used potent antihypertensive agents. Their vasodilatory effects are associated with Adverse Effects (AEs) such as peripheral edema, headache and flushing.

The incidence of peripheral edema with Calcium Channel Blocker (CCB) is 6% in a recent systematic review and is clearly dose-dependent and more common in women, in obese and in elderly hypertensives. Peripheral edema could be a cause for poor persistence with therapy or antihypertensive treatment withdrawal and has a deleterious impact on health-related quality of life.

A recent meta-analysis of head-to-head trials to compare the efficacy and safety profile of manidipine and amlodipine showed significantly better safety of manidipine: the Relative Risk (RR) for adverse event was 0.69 (0.56-0.85), and particularly for ankle edema Relative Risk (RR) was 0.35 (0.22-0.54).

Although peripheral edema is an important issue in Calcium Channel Blocker (CCB) treatment, techniques (e.g, ankle-foot volume using a water displacement measurement, plethysmography, and pretibial subcutaneous tissue pressure) for the objective measurement are not generally available in a clinical setting. Most clinical studies relied on self-report of peripheral edema that is not a reliable objective method.

Recently, Bioelectrical Impedance Analysis (BIA) has become increasingly popular for estimating body composition, including Extracellular Water (ECW) and Intracellular Water (ICW), fat mass and fat-free mass. Mechanistically, the Calcium Channel Blocker (CCB)-related peripheral edema is likely due to distal arteriolar dilatation with capillary leak to tissue spaces. Because BIA method can measure the edema as the ratio of Extracellular Water (ECW) to Total Body Water (TBW), it may reflect the Calcium Channel Blocker (CCB)-related edema. Moreover, the Direct Segmental Multi-frequency Bioelectrical Impedance Analysis (DSM-BIA) has been validated to assess segmental body (i.e., trunk, arms and legs) composition in addition to total body composition and can provide segmental edema score as well as total edema score. This new, previously not reported method is expected to provide more objective and precise data for peripheral edema.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
  1. Manidipine 20mg/day, Amlodipine 10mg/day
  2. Sealed envelope method randomization according to gender and age

    • 25 males under 55 years old
    • 25 males more than 55 years old
    • 25 females under 55 years old
    • 25 females more than 55 years old
Masking: Single (Participant)
Masking Description: Blinded-endpoint
Primary Purpose: Treatment
Official Title: Manidipine Versus Amlodipine in Patients With Hypertension: Effects on Peripheral Edema Evaluated by Bioimpedance Analysis
Actual Study Start Date : August 20, 2015
Actual Primary Completion Date : May 15, 2018
Actual Study Completion Date : August 14, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

Arm Intervention/treatment
Experimental: Manidipine 20mg
50 patients will be administered orally manidipine 20mg/day after 1~2 week run-in period
Drug: Manidipine 20mg

After a 1~2-week run-in period, patents will be randomized to receive manidipine (20 mg/day; n=50) for a 8-week open-labeled phase. Study drugs will be administered orally and once daily between 8:00am and 10:00am.

BP, heart rate, adverse events and concomitant therapy are assessed and a physical examination is performed at each visit. A 12-lead standard ECG is obtained and hematology, clinical biochemistry and urine analysis investigations performed at the screening visit. A Bioelectrical Impedance Analysis (BIA) is undertaken at the screening visit and at the end of the 8-week treatment course. Patients have to attend the clinic visit every 4 weeks during the treatment period.

Other Name: Madipine Tab(Manidipine Hydrochloride) 20mg (CJ)

Active Comparator: Amlodipine 10mg
50 patients will be administered orally amlodipine 10mg/day after 1~2 week run-in period
Drug: Amlodipine 10mg

After a 1~2-week run-in period, patents will be randomized to receive amlodipine (10 mg/day; n=50) for a 8-week open-labeled phase. Study drugs will be administered orally and once daily between 8:00am and 10:00am.

BP, heart rate, adverse events and concomitant therapy are assessed and a physical examination is performed at each visit. A 12-lead standard ECG is obtained and hematology, clinical biochemistry and urine analysis investigations performed at the screening visit. A Bioelectrical Impedance Analysis (BIA) is undertaken at the screening visit and at the end of the 8-week treatment course. Patients have to attend the clinic visit every 4 weeks during the treatment period.

Other Name: Amlodipine Pfizer 10mg (Pfizer)




Primary Outcome Measures :
  1. Change in leg edema score (Extracellular Water(ECW) to Total Body Water(TBW)) [ Time Frame: Up to 8 weeks ]

Secondary Outcome Measures :
  1. Changes in segmental (each arm/leg, trunk) edema score [ Time Frame: Up to 8 weeks ]
  2. Changes in Blood Pressure (BP) [ Time Frame: Up to 8 weeks ]
  3. Incidences of AEs [ Time Frame: Up to 8 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female outpatients between the ages of 20 and 80 years with uncomplicated essential hypertension are eligible.
  • Inclusion criteria requires that patients have either stage I or stage II hypertension (mean sitting systolic Blood Pressure (BP) 140-179 mmHg, diastolic BP 90-109 mmHg).
  • The patients are newly diagnosed or known hypertensive subjects who were not taking antihypertensive agents for more than the last 4 weeks.

Exclusion Criteria:

  • Patients are excluded from the study if they have any evidence of clinically significant concurrent medical conditions including cardiac, renal, hepatic, gastrointestinal, or endocrinologic disease.
  • Patients are also excluded if they have known hypersensitivity or serious drug reactions to Calcium Channel Blockers (CCBs), any evidence of prior deep vein thrombosis, lymphatic disease, or concurrent requirement for medications that could affect Blood Pressure (BP) or salt and water retention (e.g, nonsteroidal antinflammatory drugs, estrogen containing drugs).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03106597


Locations
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Korea, Republic of
Yonsei University Severance Hospital
Seoul, Korea, Republic of, 03722
Korea University Guro Hospital
Seoul, Korea, Republic of, 08308
Yonsei University Wonju Hospital
Wonju, Korea, Republic of, 26426
Sponsors and Collaborators
Korea University Guro Hospital
Takeda Pharmaceuticals International, Inc.
Investigators
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Principal Investigator: Eung Ju Kim, MD Professor
Publications:

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Responsible Party: Eung Ju Kim, Professor, Korea University Guro Hospital
ClinicalTrials.gov Identifier: NCT03106597    
Other Study ID Numbers: KUGH15082 (MAAMA)
First Posted: April 10, 2017    Key Record Dates
Last Update Posted: September 4, 2020
Last Verified: April 2017
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
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Eung Ju Kim, Korea University Guro Hospital:
Peripheral Edema
Bioimpedance Analysis
Additional relevant MeSH terms:
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Hypertension
Vascular Diseases
Cardiovascular Diseases
Amlodipine
Manidipine
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents