Manidipine Versus Amlodipine in Patients With Hypertension

September 2, 2020 updated by: Eung Ju Kim, Korea University Guro Hospital

Manidipine Versus Amlodipine in Patients With Hypertension: Effects on Peripheral Edema Evaluated by Bioimpedance Analysis

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 08308
        • Korea University Guro Hospital
      • Seoul, Korea, Republic of, 03722
        • Yonsei University Severance Hospital
      • Wonju, Korea, Republic of, 26426
        • Yonsei University Wonju Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Amlodipine Pfizer 10mg (Pfizer)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in leg edema score (Extracellular Water(ECW) to Total Body Water(TBW))
Time Frame: Up to 8 weeks
Up to 8 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Changes in segmental (each arm/leg, trunk) edema score
Time Frame: Up to 8 weeks
Up to 8 weeks
Changes in Blood Pressure (BP)
Time Frame: Up to 8 weeks
Up to 8 weeks
Incidences of AEs
Time Frame: Up to 8 weeks
Up to 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Korea University Guro Hospital

Collaborators

Takeda Pharmaceuticals International, Inc.

Investigators

  • Principal Investigator: Eung Ju Kim, MD, professor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 20, 2015

Primary Completion (Actual)

May 15, 2018

Study Completion (Actual)

August 14, 2019

Study Registration Dates

First Submitted

March 29, 2017

First Submitted That Met QC Criteria

April 4, 2017

First Posted (Actual)

April 10, 2017

Study Record Updates

Last Update Posted (Actual)

September 4, 2020

Last Update Submitted That Met QC Criteria

September 2, 2020

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KUGH15082 (MAAMA)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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