Essential HypertensionPhase 2/3NCT01956786
Efficacy of Amlodipine-Folic Acid Tablets on Reduction of Blood Pressure and Plasma Homocysteine
A Phase 2/3 study testing Amlodipine-FA tablet,low dose group, Amlodipine-FA tablet,high dose group and Amlodipine in people with Essential Hypertension, run by Shenzhen Ausa Pharmed Co.,Ltd at 3 sites in China.
Trial summary
To evaluate the efficacy of Amlodipine-Folic Acid Tablets on reduction of blood pressure and plasma total homocysteine. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Essential Hypertension
- What is being tested?
- Amlodipine-FA tablet,low dose group, Amlodipine-FA tablet,high dose group and Amlodipine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 540 participants
- Where
- 3 sitesChina
- Study dates
- Sep 2013to Feb 2014
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18-75 years;
- Sedentary systolic blood pressure between 140 mmHg and 180 mmHg, and/or sedentary diastolic blood pressure between 90 mmHg and 110 mmHg;
- Plasma homocysteine ≥ 10μmol/L;
- ACEI-intolerance
- Signed the written informed consent.
Who cannot join
- Pregnant women or women within lactation period;
- Hypersensitive to Calcium Channel Blocker (CCB) or folic acid;
- Easily hypersensitiveness;
- Diagnosed secondary hypertension or skeptical secondary hypertension;
- Severe hypertension (sedentary systolic blood pressure greater than or equal to 180 mmHg and/or sedentary diastolic blood pressure greater than or equal to 110 mmHg)
- Severe diseases:
Show all 18Show fewer
- Cardiovascular system:Diagnosed cardia insufficiency (New York Health Association [NYHA] Ⅲ level and higher);Hypertrophic obstructive cardiomyopathy (HOCM);Clinical significantly Valvular Disease of the Heart (VDH);Acute coronary syndrome or coronary artery interventional therapy or coronary artery bypass graft within three months;Severe arrhythmia such as atrial flutter, atrial fibrillation, atrioventricular block above Ⅱlevel, et al;
- Alimentary system:Active virus hepatitis;Any of alanine aminotransferase (ALT), aspartate aminotransferase (AST), galactosylhydroxylysyl glucosyltransferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), Direct Bilirubin (DB) was above 2 times of it's normal value upper limit, albumin (ALB) greater than 30 g/L;Stomach bulk resect and gastrojejunostomy;Stomach intestine malabsorption;
- Urinary system:Serum creatinine greater than or equal to 200 mmol/L;Diagnosed stenosis of renal artery, solitary kidney;Renal transplantation;
- Endocrine system:Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (fasting glucose greater than or equal to 11.1 mmol/L);Diagnosed and uncontrolled hyperthyrosis;
- Respiratory system:Pulmonary Heart Disease;Chronic Obstructive Pulmonary Disease(COPD);
- Neuropsychiatric system:Transient Ischemia Attach (TIA) or stroke within 3 months;Severe peripheral nerve or vegetative nerve functional disturbance; Psyche or nervous system dysfunction;Drugs or alcohol dependence;
- Others:Malignant tumor, malnutrition, haematogenesis dysfunction, et al;
- Obviously abnormal laboratory examination or signs;
- Taking other antihypertensive drugs and unwilling to stop;
- Taking folic acid or other Vitamin B groups and unwilling to stop;
- Ever to participant in any drug trial not yet approved within 4 weeks before the first visit.
- -
Trial locations and contacts
3 sites in 1 country.
China3 sites, 3 recruiting
- Recruiting
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006
Cheng Xiaoshu, MD, 86-791-6268844, xiaoshumenfan@126.com
Cheng Xiaoshu, MD
- Recruiting
Ruijin Hospital, Shanghai Jiao Tong Univesity
Shanghai, Shanghai Municipality, 310000
Wang Jiguang, MD, 86-021-64370045, jiguangw@gmail.com
Wang Jiguang, MD
- Not yet recruiting
The Affiliated Hospital of Xuzhou Medical College
Xuzhou, Jiangsu, 221006
Wang Zhirong, MD, 86-0516-85802111, xzzrw@163.com
Wang Zhirong, MD
About this study
Official title: Efficacy of Amlodipine-Folic Acid Tablets on Reduction of Blood Pressure and Plasma Homocysteine in Patients With Mild to Moderate Hypertension, Hyperhomocysteinemia and Angiotension-Converting Enzyme Inhibitor Intolerance
To evaluate the efficacy of Amlodipine-Folic Acid Tablets on reduction of blood pressure and plasma total homocysteine.
Read the detailed description
Traditional risk factors are estimated to account for only part of cardiovascular disease (CVD)risk. Non-traditional risk factors such as increased homocysteine concentrations are believed to be causally related to CVD. The interactive effect between hypertension and hyperhomocysteinemia on the risk of CVD has received great attention. Methylenetetrahydrofolate reductase (MTHFR)was the main regulatory enzymes for homocysteine metabolism. MTHFR converts 5,10-methylene-THF into 5-methyl-THF. Polymorphism of MTHFR C677T leads to a reduction in enzyme activity, which may lead to an increased concentration of plasma homocysteine and lower levels of serum folate, particularly in those with low folate intake. Enalapril Maleate-Folate Tablets, known to reduce both blood pressure and serum homocysteine and thereby preventing stroke, was found to have adverse events, such as cough, called ACEI-intolerance in some patients.
In the present study, we sought to assess:(1)the efficacy and safety of Amlodipine-Folic Acid Tablets in lowing blood pressure and homocysteine in patients with mild to moderate hypertension, hyperhomocysteinemia (hcy≥10μmol/L)and ACEI intolerance;(2)whether the blood pressure and homocysteine-lowing efficacy of Amlodipine-Folic Acid Tablets can be modified by individual MTHFR C677T polymorphisms.
In all, about 540 patients with mild to moderate hypertension, hyperhomocysteinemia and ACEI intolerance will be enrolled in this trial. Eligible subjects are randomly and double-blindly assigned to one of the three treatment groups:1)amlodipine tablet(5mg,control group);2)amlodipine-folic acid tablet(5mg amlodipine combined with 0.4mg of folic acid,low FA group);or 3)amlodipine-folic acid tablet (5mg amlodipine combined with 0.8mg of folic acid,high FA group),once daily for 8 weeks.
The allocation of participants was programmed by an independent statistical coordinating center,encrypted,and sent to each study center.Tablet containers were labeled only with the name of the trial and the allocated concealment number.The participants,care partners,and all staff directly involved in the trial were blinded to interventions during the period of the trial.
Demographic and clinical information were obtained at baseline. Blood pressure was examined at baseline and every two weeks for a total period of 8 weeks. Blood homocysteine and folate concentrations were examined at baseline and at 4th、8th weeks of the trial. MTHFR C677T genotypes were determined for each study subject.
All analyses will be performed according to the principle of intention to treat.
- Conditions
- Essential Hypertension
- Being tested
- Amlodipine-FA tablet,low dose group, Amlodipine-FA tablet,high dose group, Amlodipine
- Keywords
- Amlodipine, Folic Acid, Homocysteine, Blood Pressure
- Medical subject headings
- Essential Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amlodipine-FA tablet,low dose groupDrug
Also called low dose
5mg amlodipine combined with 0.4mg folic acid,once daily (Low-dose group)
Amlodipine-FA tablet,high dose groupDrug
Also called high dose
5mg amlodipine combined with 0.8mg folic acid,once daily (High-dose group)
AmlodipineDrug
Also called control
5mg amlodipine,once daily
| Study group | Role | What they receive |
|---|---|---|
| Amlodipine | Active comparator | 5mg amlodipine,once daily for 8 weeks Receives: Drug: Amlodipine |
| Amlodipine-FA tablet,low dose group | Experimental | 5mg amlodipine combined with 0.4mg of folic acid (FA),once daily for 8 weeks. Receives: Drug: Amlodipine-FA tablet,low dose group |
| Amlodipine-FA tablet,high dose group | Experimental | 5mg amlodipine combined with 0.8mg of folic acid (FA),once daily for 8 weeks. Receives: Drug: Amlodipine-FA tablet,high dose group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Combined effective rate of blood pressure and plasma homocysteine reduction
Measured: Blood pressure was examined at baseline and every 2 weeks for a total period of 8 weeks.Blood homocysteine concentrations were measured at baseline and at 4th and 8th week of the trial.
Secondary outcomes (1)
Blood pressure reduction or plasma homocysteine reduction
Measured: Blood pressure was examined at baseline and every 2 weeks of a total period of 8 weeks. Blood homocysteine concentrations was examined at baseline and at 4th and 8th week of the trial.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2013 (estimated)
- Study startSep 2013
- Primary completionDec 2013 (estimated)
- Study completionFeb 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Essential HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 540 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shenzhen Ausa Pharmed Co.,Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ruijin Hospital, Second Affiliated Hospital of Nanchang University, Xuzhou Medical University
- Responsible party
- Sponsor
- Investigators
- Wang Jiguang, MD, Principal investigator, Ruijin Hospital, Shanghai Jiao Tong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01956786
- Sponsor's protocol ID
- Ausa-Amlodipine B
- Status last verified
- Jul 2013
- First submitted
- 30 Sep 2013
- Last updated
- 8 Oct 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bao H, Huang X, Li P, Sheng C, Zhang J, Wang Z, Song D, Hu L, Ding C, Cheng Z, Yao C, Chen G, Cui Y, Qin X, Tang G, Wang X, Huo Y, Cheng X, Wang J. Combined use of amlodipine and folic acid are significantly more efficacious than amlodipine alone in lowering plasma homocysteine and blood pressure among hypertensive patients with hyperhomocysteinemia and intolerance to ACEI: A multicenter, randomized, double-blind, parallel-controlled clinical trial. J Clin Hypertens (Greenwich). 2023 Aug;25(8):689-699. doi: 10.1111/jch.14697. Epub 2023 Jul 11.
PubMed 37433173
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Amlodipine-Folic Acid Tablets on Reduction of Blood Pressure and Plasma Homocysteine in Patients With Mild to Moderate Hypertension, Hyperhomocysteinemia and Angiotension-Converting Enzyme Inhibitor Intolerance
- ClinicalTrials.gov ID
- NCT01956786
- Acronym / sponsor ID
- Ausa-Amlodipine B
- Conditions
- Essential Hypertension
- Keywords
- Amlodipine, Folic Acid, Homocysteine, Blood Pressure
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 540 participants (estimated)
- Lead sponsor
- Shenzhen Ausa Pharmed Co.,LtdIndustry (pharma, biotech, devices)
- Collaborators
- Ruijin Hospital, Second Affiliated Hospital of Nanchang University, Xuzhou Medical University
- Study start
- Sep 2013
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Feb 2014 (estimated)
- First posted
- 8 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the efficacy of Amlodipine-Folic Acid Tablets on reduction of blood pressure and plasma total homocysteine.
Detailed description
Traditional risk factors are estimated to account for only part of cardiovascular disease (CVD)risk. Non-traditional risk factors such as increased homocysteine concentrations are believed to be causally related to CVD. The interactive effect between hypertension and hyperhomocysteinemia on the risk of CVD has received great attention. Methylenetetrahydrofolate reductase (MTHFR)was the main regulatory enzymes for homocysteine metabolism. MTHFR converts 5,10-methylene-THF into 5-methyl-THF. Polymorphism of MTHFR C677T leads to a reduction in enzyme activity, which may lead to an increased concentration of plasma homocysteine and lower levels of serum folate, particularly in those with low folate intake. Enalapril Maleate-Folate Tablets, known to reduce both blood pressure and serum homocysteine and thereby preventing stroke, was found to have adverse events, such as cough, called ACEI-intolerance in some patients.
In the present study, we sought to assess:(1)the efficacy and safety of Amlodipine-Folic Acid Tablets in lowing blood pressure and homocysteine in patients with mild to moderate hypertension, hyperhomocysteinemia (hcy≥10μmol/L)and ACEI intolerance;(2)whether the blood pressure and homocysteine-lowing efficacy of Amlodipine-Folic Acid Tablets can be modified by individual MTHFR C677T polymorphisms.
In all, about 540 patients with mild to moderate hypertension, hyperhomocysteinemia and ACEI intolerance will be enrolled in this trial. Eligible subjects are randomly and double-blindly assigned to one of the three treatment groups:1)amlodipine tablet(5mg,control group);2)amlodipine-folic acid tablet(5mg amlodipine combined with 0.4mg of folic acid,low FA group);or 3)amlodipine-folic acid tablet (5mg amlodipine combined with 0.8mg of folic acid,high FA group),once daily for 8 weeks.
The allocation of participants was programmed by an independent statistical coordinating center,encrypted,and sent to each study center.Tablet containers were labeled only with the name of the trial and the allocated concealment number.The participants,care partners,and all staff directly involved in the trial were blinded to interventions during the period of the trial.
Demographic and clinical information were obtained at baseline. Blood pressure was examined at baseline and every two weeks for a total period of 8 weeks. Blood homocysteine and folate concentrations were examined at baseline and at 4th、8th weeks of the trial. MTHFR C677T genotypes were determined for each study subject.
All analyses will be performed according to the principle of intention to treat.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Amlodipine | Active comparator | Drug: Amlodipine5mg amlodipine,once daily for 8 weeks |
| Amlodipine-FA tablet,low dose group | Experimental | Drug: Amlodipine-FA tablet,low dose group5mg amlodipine combined with 0.4mg of folic acid (FA),once daily for 8 weeks. |
| Amlodipine-FA tablet,high dose group | Experimental | Drug: Amlodipine-FA tablet,high dose group5mg amlodipine combined with 0.8mg of folic acid (FA),once daily for 8 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Aged 18-75 years;
- Sedentary systolic blood pressure between 140 mmHg and 180 mmHg, and/or sedentary diastolic blood pressure between 90 mmHg and 110 mmHg;
- Plasma homocysteine ≥ 10μmol/L;
- ACEI-intolerance
- Signed the written informed consent.
Key exclusion criteria (18 listed)
- Pregnant women or women within lactation period;
- Hypersensitive to Calcium Channel Blocker (CCB) or folic acid;
- Easily hypersensitiveness;
- Diagnosed secondary hypertension or skeptical secondary hypertension;
- Severe hypertension (sedentary systolic blood pressure greater than or equal to 180 mmHg and/or sedentary diastolic blood pressure greater than or equal to 110 mmHg)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Amlodipine-FA tablet,low dose groupAlso: low dose5mg amlodipine combined with 0.4mg folic acid,once daily (Low-dose group) | Drug | Amlodipine-FA tablet,low dose group |
| Amlodipine-FA tablet,high dose groupAlso: high dose5mg amlodipine combined with 0.8mg folic acid,once daily (High-dose group) | Drug | Amlodipine-FA tablet,high dose group |
| AmlodipineAlso: control5mg amlodipine,once daily | Drug | Amlodipine |
Primary outcome
Combined effective rate of blood pressure and plasma homocysteine reduction
Time frame: Blood pressure was examined at baseline and every 2 weeks for a total period of 8 weeks.Blood homocysteine concentrations were measured at baseline and at 4th and 8th week of the trial.
1 secondary outcome
Blood pressure reduction or plasma homocysteine reduction
Time frame: Blood pressure was examined at baseline and every 2 weeks of a total period of 8 weeks. Blood homocysteine concentrations was examined at baseline and at 4th and 8th week of the trial.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2013.
- Derived from this study: PubMed 37433173Bao H, Huang X, Li P, Sheng C, Zhang J, Wang Z, Song D, Hu L, Ding C, Cheng Z, Yao C, Chen G, Cui Y, Qin X, Tang G, Wang X, Huo Y, Cheng X, Wang J. Combined use of amlodipine and folic acid are significantly more efficacious than amlodipine alone in lowering plasma homocysteine and blood pressure among hypertensive patients with hyperhomocysteinemia and intolerance to ACEI: A multicenter, randomized, double-blind, parallel-controlled clinical trial. J Clin Hypertens (Greenwich). 2023 Aug;25(8):689-699. doi: 10.1111/jch.14697. Epub 2023 Jul 11.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The Second Affiliated Hospital of Nanchang University
Nanchang, China
Wang Jiguang, MD principal investigator
Ruijin Hospital, Shanghai Jiao Tong University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Amlodipine-FA tablet,low dose group, Amlodipine-FA tablet,high dose group and Amlodipine in people with Essential Hypertension, run by Shenzhen Ausa Pharmed Co.,Ltd at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Combined effective rate of blood pressure and plasma homocysteine reduction (time frame: Blood pressure was examined at baseline and every 2 weeks for a total period of 8 weeks.Blood homocysteine concentrations were measured at baseline and at 4th and 8th week of the trial.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01956786, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2013.