A Phase 4 interventional study of Folic Acid and Enalapril Maleate and Folic Acid Tablets (Yiye) in Hypertension, sponsored by Shenzhen Ausa Pharmed Co.,Ltd. Status unknown at 5 sites in China. Open to participants aged 45 Years and older. Per ClinicalTrials.gov, last updated 2018-07-18.
Sponsored by Shenzhen Ausa Pharmed Co.,Ltd · Phase 4, Interventional, and Treatment
This is a multicenter, randomized, double-blind, controlled clinical trial. It aims to investigate the effects of different doses of folic acid on lowering homocysteine (Hcy) in patients with hypertension with different genotypes of MTHFR C677T and to determine a dose-response relationship.
This study consists of 3 phases: screening ( 2-10 days ), run-in period (0-2 weeks), and double-blind treatment (8 weeks). Follow-up visits will take place at the beginning of both the run-in period and the double-blind treatment period, and at the end of the 2nd, 4th, 6th, and 8th weeks. Hypertensive patients demonstrating good tolerance and adherence to angiotensin converting enzyme inhibitor (ACEI) drugs and who have already been genotyped for MTHFR C677T polymorphism may pass over the run-in period and directly enter the double-blind randomized treatment period. No medications that could affect the assessment of efficacy may be taken during any stage of the study.
Phase I: Screening（V0）
Phase I takes place for about 2-10 days. The purpose is to obtain informed consent and make a preliminary assessment of the patient.
At the first screening visit (V0), or prior to the official treatment visit, a clinical examination will be performed to determine the patient's clinical diagnosis and to determine eligibility for inclusion in the study. General demographic information and questions related to the inclusion/exclusion criteria of this study will be obtained. Additionally, this will be the time to discuss the impact of participant vacation/travel plans on adherence and compliance with the trial protocol.
Before carrying out any research procedures, the purpose of the study and study procedures will be explained and the participant's informed consent will be obtained.
Clinical Diagnosis and Assessment: Prior to the start of the Run-in Period, baseline data and efficacy evaluation data will be collected according to the study flow chart; blood and urine samples will also be collected.
Blood Pressure Measurement: A unified electronic sphygmomanometer blood pressure measurement will be obtained. Participants will be prohibited from smoking, drinking coffee or tea, and urinating 30 minutes prior. Before taking the measurement, participants will be asked to sit quietly for at least 5 minutes prior; the participant will then be asked to assume a sitting position, with both feet flat on the ground and the upper right arm exposed and at the same height as the heart. After measurement, the sphygmomanometer will display the blood pressure and pulse. The average of 3 consecutive measurements with 1-2 minutes between each measurement will be taken and recorded. The median of 3 pulse measurements will also be recorded.
Laboratory Tests: Female participants of childbearing age must undergo a pregnancy test prior to the run-in period. Based on clinical indications, the investigator may also decide to conduct a pregnancy test at any time throughout the trial as needed. All participants will be asked to complete the following laboratory tests: 12-lead ECG, urinalysis, blood biochemistry, folate, and Hcy assessment during the screening period. All results will be obtained prior to the run-in period visit.
Phase Ⅱ: Run-in Period (V1-V2)
All eligible patients will begin a treatment of enalapril (10mg/d) for a 0 to 2-week open induction period, during which time other antihypertensive drugs may also be concurrently used. MTHFR C677T genotype will also be determined during this phase. The primary purpose of this phase is to assess participant compliance to the enalapril treatment regimen as well as to observe the participant's tolerance to enalapril, so as to avoid including those participants with poor compliance or intolerance to enalapril to the double-blind treatment phase.
Newly diagnosed hypertensives should be given enalapril during the run-in period and can be given other antihypertensive drugs at the clinician's discretion. For hypertensive patients currently using medication, if not currently using enalapril, the clinician should, based on the patient's medical condition, add or switch the patient's medication to enalapril.
Hypertensive patients demonstrating good tolerance and adherence to angiotensin converting enzyme inhibitor (ACEI) drugs and who have already been genotyped for MTHFR C677T polymorphism may pass over the run-in period and directly enter the double-blind randomized treatment period.
Phase Ⅲ: Double-Blind Treatment (V2-V6)
The third phase consists of 8 weeks of a randomized, double-blind treatment. Patients who remain eligible for participation in the study will first be stratified by gender and MTHFR C677T genotype (CC, CT, TT), for a total of 6 strata at the start of V2. Each of the 6 strata will then be randomized into 8 treatment groups: either enalapril only (10mg), or one of the other 7 treatment combinations with various doses of folic acid. During the 8-week double-blind treatment period, other antihypertensive drugs can be combined with the treatment drug to achieve blood pressure control; the patient will be followed-up every 2 weeks during the treatment period, and the treatment drug will be distributed at each visit. During this period, participants should continue to avoid taking medications that may interfere with the evaluation of treatment efficacy.
For participants who complete the run-in period and are eligible to remain in the study, a randomized treatment allocation list will be generated using a stratified, block-wise, randomized approach by MTHFR C677T genotype and gender. This list will assign a unique study ID to every study participant. The ID corresponds to a specific treatment allocation; this ID assignment determines the treatment type the participant will receive.
This study will use a two-level blinding procedure. The first level of blinding will generate a randomized sequence table corresponding each study ID to one of the eight different treatment groups. Each treatment will be given a treatment group code (from a to h) so that the actual treatment cannot be identified from this table. The second level of blinding will denote the type of treatment that corresponds to each of the eight different coded treatment groups (a through h) that were generated from the first level of blinding. The randomized ID's will be generated by a statistical analysis group; the blinding program and all electronic documents regarding the level one and two blinding will be sealed in separate envelopes and protected by the sponsor. The seal cannot be broken before the trial officially undergoes the unblinding process. In addition, the research drug management center will maintain a copy of the treatment allocation list and will be responsible for encoding the treatment drugs and dispensing the medications to the participants based on the treatment allocation list.
6,114 studies on the registry are indexed under Hypertension; 912 are open to participants now.
This study's planned enrollment of 3,600 is above the median of 100 across 4,575 interventional studies indexed under Hypertension.
Browse Hypertension studies →Shenzhen Ausa Pharmed Co.,Ltd is the lead sponsor of 7 studies on the registry; 2 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Inclusion Criteria for Double-Blind Treatment Period:
Exclusion Criteria:
Participants meeting any of the following criteria may not participate in this study:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Enalapril Maleate (10mg) with 0 mg folic acid
Drug: Folic Acid · Drug: Enalapril
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.4mg)
Drug: Folic Acid · Drug: Enalapril Maleate and Folic Acid Tablets (Yiye)
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.4mg) with 0.2 mg folic acid
Drug: Folic Acid · Drug: Enalapril Maleate and Folic Acid Tablets (Yiye)
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg)
Drug: Folic Acid · Drug: Enalapril Maleate and Folic Acid Tablets (Yiye)
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg) with 0.4 mg folic acid
Drug: Folic Acid · Drug: Enalapril Maleate and Folic Acid Tablets (Yiye)
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg) with 0.8 mg folic acid
Drug: Folic Acid · Drug: Enalapril Maleate and Folic Acid Tablets (Yiye)
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg) with 1.2 mg folic acid
Drug: Folic Acid · Drug: Enalapril Maleate and Folic Acid Tablets (Yiye)
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg) with 1.6 mg folic acid
Drug: Folic Acid · Drug: Enalapril Maleate and Folic Acid Tablets (Yiye)
Folic acid used in this study are listed products. All drugs used in the double-blind treatment period of this study will be loaded into safety capsules with the same outer appearance; all parties involved in the trial will be unaware of the contents of the capsules.
Drug pages: Enalapril · Folic Acid
Enalapril Maleate and Folic Acid Tablets (Yiye) have been approved for listing by the China Food and Drug Administration. Approval number: Zhunzi H20103723.All drugs used in the double-blind treatment period of this study will be loaded into safety capsules with the same outer appearance; all parties involved in the trial will be unaware of the contents of the capsules.
Enalapril used in this study are listed products. All drugs used in the double-blind treatment period of this study will be loaded into safety capsules with the same outer appearance; all parties involved in the trial will be unaware of the contents of the capsules.
Percentage decrease in blood homocysteine levels by the end of the 8th week from baseline.
Hcy percent decrease =（baseline Hcy - end Hcy) /baseline Hcy \*100%
Time frame: by the end of the 8th week from the baseline
Magnitude of decrease in blood homocysteine by the end of the 8th week from baseline.
Absolute Hcy reduction (μmol/L) = baseline Hcy - end Hcy
Time frame: by the end of the 8th week from the baseline
Percentage of increase in blood folate levels by the end of the 8th week from baseline.
Folate increase rate=(end folate- baseline folate)/baseline folate \*100% folate increase magnitude= end folate - baseline folate
Time frame: by the end of the 8th week from the baseline
Magnitude of increase in blood folate levels by the end of the 8th week from baseline.
Absolute folate reduction (μmol/L)= baseline folate - end folate
Time frame: by the end of the 8th week from the baseline
Plan to share: Undecided
This study is status unknown, as verified in Jul 2018. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Enalapril · Folic Acid
Shenzhen Ausa Pharmed Co.,Ltd