HypertensionPhase 4GIANTNCT01066039
Phase 4 Study to Assess the Effect of Bisoprolol on Glycemic Level in Type II Diabetic Subjects With Suboptimal Blood Pressure Control
A Phase 4 study testing Bisoprolol in people with Hypertension and Diabetes Mellitus, Type II, run by Merck KGaA, Darmstadt, Germany at 1 site in South Korea.
Trial summary
This is a 24-week, prospective, multicenter, open-label, single-arm study to assess the effect of bisoprolol on glycemic level in Type 2 diabetes mellitus (T2DM) controlled subjects with hypertension. Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Hypertension, Diabetes Mellitus, Type II
- What is being tested?
- Bisoprolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 202 participants
- Where
- 1 siteSouth Korea
- Study dates
- Apr 2010to Apr 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age of 20 years or older and less than 80 years
- Subjects with T2DM
- Subjects who have failed to achieve an appropriate BP level as a result of treatment with any antihypertensive drug other than beta blockers - that is, with BP inadequately controlled to greater than or equal to (>=) 130/80 mmHg. However, those who have used a beta blocker before 12 weeks can be enrolled
- Subjects who underwent stable anti-diabetic regimen during the 12 weeks prior to screening
- Signed written informed consent
Who cannot join
- Ongoing insulin therapy
- Change in two HbA1c levels measured at an interval of 4 weeks or longer for the previous 6 months is at least 1% (the last HbA1c is measured within 4 weeks)
- Secondary hypertension
- Subjects with renal impairment (creatinine greater than 150 micromol per liter or 1.7 milligram per deciliter)
- Cardiovascular disease (uncontrolled or symptomatic arrhythmia, unstable angina, sick sinus syndrome, second or third degree atrioventricular (AV) block, bradycardia [less than 50 beats per minute], congestive heart failure, myocardial infarction, cerebral infraction attached within 12 weeks)
- Subjects requiring BP control by at least 3 different antihypertensive drugs, or with either systolic blood pressure (SBP) >=180 mmHg or diastolic blood pressure (DBP) >=110 mmHg at baseline
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- Subjects with type 1 diabetes mellitus (T1DM)
- Uncontrolled diabetes with HbA1c >9%
- BMI >40 kilogram per square meter (kg/m^2)
- Pulmonary disease (chronic obstructive pulmonary disease [COPD], bronchial asthma)
- Other patients considered by the investigator to be not eligible for participation in this study for a legal or mental reason
- Contraindications for beta-blocker
- Pregnant or lactating women
- Use of an investigational drug within 30 days of entry to the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective, Multi-center, Open-label, Single Arm Study to Assess the Effect of Bisoprolol on Glycemic Level in Type II DIAbetic patieNTs With Suboptimal Blood Pressure Control (GIANT Study)
This is a 24-week, prospective, multicenter, open-label, single-arm study to assess the effect of bisoprolol on glycemic level in Type 2 diabetes mellitus (T2DM) controlled subjects with hypertension. The hypothesis of study is that there is no change in glycemic level and lipid metabolism as determined by glycosylated hemoglobin (HbA1c) using bisoprolol in T2DM subjects with suboptimal blood pressure (BP) control.
Read the detailed description
Diabetes mellitus and hypertension are two of the most common chronic conditions, and each predisposes to accelerated atherosclerosis, cardiovascular disease, and death. There has been a concern that beta-blocker might have adverse effects in subjects with diabetes on glucose metabolism, but some data shows that highly beta-1 selective agents such as bisoprolol are essentially free of metabolic disturbances involving blood sugar, insulin sensitivity and lipids.
This is a prospective, multicenter, single-arm, open-label study to assess the glycemic effect of bisoprolol in T2DM subjects with suboptimal BP control.
After pre-screening period, each enrolled subject with T2DM and suboptimal BP control will undergo laboratory test for efficacy and safety measurement. After that, subject will continue his/her usual dosage of antihypertensive medication and bisoprolol will be added.
Subjects will be instructed to continue their diet and level of physical activity and to attempt to maintain current body weight until completion of the study.
Bisoprolol will be titrated upward until a dosage that lowers BP to less than 130/80 millimeter of mercury (mmHg) during the first 2 months of treatment. The maximum dosage of bisoprolol will be 10 mg once daily. Following 6 month of added bisoprolol therapy, all efficacy and safety measurements will be repeated.
The duration of study will be up to 24 weeks for each subject.
Objectives
Primary objective:
- To assess the effect of bisoprolol on glycemic control measured by change from baseline in HbA1c in T2DM subjects with suboptimal BP control
Secondary objectives:
- To evaluate the effects of bisoprolol, as add-on therapy, on BP in T2DM subjects with suboptimal BP control
- To evaluate the effects of bisoprolol, as add-on therapy, on insulin sensitivity as determined by Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)
- To evaluate the effects of bisoprolol, as add-on therapy, on lipid metabolism as determined by lipid profile in T2DM subjects with suboptimal BP control
- To evaluate the safety and tolerability of bisoprolol in T2DM subjects with suboptimal BP control
- To assess the effects of bisoprolol combination therapy on insulin and c-peptide in T2DM subjects with suboptimal BP control compared to baseline
- To assess the effects of bisoprolol combination therapy on microalbumin and albumin/creatinine ratio in T2DM subjects with suboptimal BP control compared to baseline
- Conditions
- Hypertension, Diabetes Mellitus, Type II
- Being tested
- Bisoprolol
- Keywords
- Bisoprolol, Hypertension, Diabetes mellitus, Type II, Blood pressure, Glycemic level
- Medical subject headings
- Hypertension, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BisoprololDrug
Also called Concor, Concor Plus, ConcorCor, Lodoz
Bisoprolol tablet will be administered orally at dose of 5 milligram (mg) once daily for 24 weeks. If the blood pressure is not less than 130/80 millimeter of mercury (mmHg) during the first 8 weeks of treatment (up-titration), then the dose will be adjusted to 10 mg daily. In cases of hypotensive effect, symptomatic bradycardia or arrhythmia, the daily dose will be reduced to 2.5 mg.
| Study group | Role | What they receive |
|---|---|---|
| Bisoprolol | Experimental | Not described Receives: Drug: Bisoprolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Month 6
HbA1c represents the percentage of glycosylated hemoglobin. The change in HbA1c at Month 6 was calculated as HbA1c at Month 6 minus HbA1c at baseline.
Measured: Baseline, Month 6
Secondary outcomes (9)
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Month 3
HbA1c represents the percentage of glycosylated hemoglobin. The change in HbA1c at Month 3 was calculated as HbA1c at Month 3 minus HbA1c at baseline.
Measured: Baseline, Month 3
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Blood Pressure (BP) at Month 6
The change in SBP, DBP, and mean BP at Month 6 were calculated as SBP, DBP, and mean BP at Month 6 minus SBP, DBP, and mean BP at baseline, respectively. Mean BP was calculated using the formula: (DBP plus [{SBP minus DBP} divided by 3]).
Measured: Baseline, Month 6
Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Months 3 and 6
HOMA-IR is as an indicator of insulin resistance in participants with Type 2 diabetes mellitus and comorbid hypertension. HOMA-IR was derived from fasting plasma glucose (FPG) and fasting insulin (FI) using the formula: (FI [micro international units per milliliter {mcIU/mL}] * FPG [millimole per liter {mmol/L}]) divided by 22.5. The change in HOMA-IR at Months 3 and 6 was calculated as HOMA-IR at Months 3 and 6 minus HOMA-IR at baseline.
Measured: Baseline, Months 3 and 6
Change From Baseline in Insulin Level at Months 3 and 6
The change in insulin level at Months 3 and 6 was calculated as insulin level at Months 3 and 6 minus insulin level at baseline.
Measured: Baseline, Months 3 and 6
Change From Baseline in C-Peptide Level at Months 3 and 6
The change in C-peptide level at Months 3 and 6 was calculated as C-peptide level at Months 3 and 6 minus C-peptide level at baseline.
Measured: Baseline, Months 3 and 6
Change From Baseline in Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol and Triglyceride Level at Month 6
The change in total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and triglyceride levels at Month 6 was calculated as total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels at Month 6 minus total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels at baseline, respectively.
Measured: Baseline, Month 6
Change From Baseline in Albumin/Creatinine Ratio at Month 6
The change in albumin/creatinine ratio at Month 6 was calculated as albumin/creatinine ratio at Month 6 minus albumin/creatinine ratio at baseline.
Measured: Baseline, Month 6
Change From Baseline in Microalbumin Level at Month 6
The change in microalbumin level at Month 6 was calculated as microalbumin level at Month 6 minus microalbumin level at baseline.
Measured: Baseline, Month 6
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Measured: Baseline up to Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2010 (estimated)
- Study startApr 2010
- Primary completionApr 2013
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 202 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Ltd.
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01066039
- Sponsor's protocol ID
- EMR 200006-509
- Acronym
- GIANT
- Status last verified
- Jun 2014
- First submitted
- 8 Feb 2010
- Last updated
- 4 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 4 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multi-center, Open-label, Single Arm Study to Assess the Effect of Bisoprolol on Glycemic Level in Type II DIAbetic patieNTs With Suboptimal Blood Pressure Control (GIANT Study)
- ClinicalTrials.gov ID
- NCT01066039
- Acronym / sponsor ID
- GIANT / EMR 200006-509
- Conditions
- Hypertension, Diabetes Mellitus, Type II
- Keywords
- Bisoprolol, Hypertension, Diabetes mellitus, Type II, Blood pressure, Glycemic level
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 202 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Collaborators
- Merck Ltd.
- Study start
- Apr 2010
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 10 Feb 2010 (estimated)
- Results
- Posted 4 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 24-week, prospective, multicenter, open-label, single-arm study to assess the effect of bisoprolol on glycemic level in Type 2 diabetes mellitus (T2DM) controlled subjects with hypertension. The hypothesis of study is that there is no change in glycemic level and lipid metabolism as determined by glycosylated hemoglobin (HbA1c) using bisoprolol in T2DM subjects with suboptimal blood pressure (BP) control.
Detailed description
Diabetes mellitus and hypertension are two of the most common chronic conditions, and each predisposes to accelerated atherosclerosis, cardiovascular disease, and death. There has been a concern that beta-blocker might have adverse effects in subjects with diabetes on glucose metabolism, but some data shows that highly beta-1 selective agents such as bisoprolol are essentially free of metabolic disturbances involving blood sugar, insulin sensitivity and lipids.
This is a prospective, multicenter, single-arm, open-label study to assess the glycemic effect of bisoprolol in T2DM subjects with suboptimal BP control.
After pre-screening period, each enrolled subject with T2DM and suboptimal BP control will undergo laboratory test for efficacy and safety measurement. After that, subject will continue his/her usual dosage of antihypertensive medication and bisoprolol will be added.
Subjects will be instructed to continue their diet and level of physical activity and to attempt to maintain current body weight until completion of the study.
Bisoprolol will be titrated upward until a dosage that lowers BP to less than 130/80 millimeter of mercury (mmHg) during the first 2 months of treatment. The maximum dosage of bisoprolol will be 10 mg once daily. Following 6 month of added bisoprolol therapy, all efficacy and safety measurements will be repeated.
The duration of study will be up to 24 weeks for each subject.
Objectives
Primary objective:
- To assess the effect of bisoprolol on glycemic control measured by change from baseline in HbA1c in T2DM subjects with suboptimal BP control
Secondary objectives:
- To evaluate the effects of bisoprolol, as add-on therapy, on BP in T2DM subjects with suboptimal BP control
- To evaluate the effects of bisoprolol, as add-on therapy, on insulin sensitivity as determined by Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)
- To evaluate the effects of bisoprolol, as add-on therapy, on lipid metabolism as determined by lipid profile in T2DM subjects with suboptimal BP control
- To evaluate the safety and tolerability of bisoprolol in T2DM subjects with suboptimal BP control
- To assess the effects of bisoprolol combination therapy on insulin and c-peptide in T2DM subjects with suboptimal BP control compared to baseline
- To assess the effects of bisoprolol combination therapy on microalbumin and albumin/creatinine ratio in T2DM subjects with suboptimal BP control compared to baseline
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bisoprolol | Experimental | Drug: Bisoprolol |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age of 20 years or older and less than 80 years
- Subjects with T2DM
- Subjects who have failed to achieve an appropriate BP level as a result of treatment with any antihypertensive drug other than beta blockers - that is, with BP inadequately controlled to greater than or equal to (>=) 130/80 mmHg. However, those who have used a beta blocker before 12 weeks can be enrolled
- Subjects who underwent stable anti-diabetic regimen during the 12 weeks prior to screening
- Signed written informed consent
Key exclusion criteria (14 listed)
- Ongoing insulin therapy
- Change in two HbA1c levels measured at an interval of 4 weeks or longer for the previous 6 months is at least 1% (the last HbA1c is measured within 4 weeks)
- Secondary hypertension
- Subjects with renal impairment (creatinine greater than 150 micromol per liter or 1.7 milligram per deciliter)
- Cardiovascular disease (uncontrolled or symptomatic arrhythmia, unstable angina, sick sinus syndrome, second or third degree atrioventricular (AV) block, bradycardia [less than 50 beats per minute], congestive heart failure, myocardial infarction, cerebral infraction attached within 12 weeks)
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 |
|---|---|---|
| BisoprololAlso: Concor, Concor Plus, ConcorCor, LodozBisoprolol tablet will be administered orally at dose of 5 milligram (mg) once daily for 24 weeks. If the blood pressure is not less than 130/80 millimeter of mercury (mmHg) during the first 8 weeks of treatment (up-titration), then the dose will be adjusted to 10 mg daily. In cases of hypotensive effect, symptomatic bradycardia or arrhythmia, the daily dose will be reduced to 2.5 mg. | Drug | Bisoprolol |
Primary outcome
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Month 6
Time frame: Baseline, Month 6
HbA1c represents the percentage of glycosylated hemoglobin. The change in HbA1c at Month 6 was calculated as HbA1c at Month 6 minus HbA1c at baseline.
9 secondary outcomes
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Month 3
Time frame: Baseline, Month 3
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Blood Pressure (BP) at Month 6
Time frame: Baseline, Month 6
Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Months 3 and 6
Time frame: Baseline, Months 3 and 6
Change From Baseline in Insulin Level at Months 3 and 6
Time frame: Baseline, Months 3 and 6
Change From Baseline in C-Peptide Level at Months 3 and 6
Time frame: Baseline, Months 3 and 6
Change From Baseline in Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol and Triglyceride Level at Month 6
Time frame: Baseline, Month 6
Change From Baseline in Albumin/Creatinine Ratio at Month 6
Time frame: Baseline, Month 6
Change From Baseline in Microalbumin Level at Month 6
Time frame: Baseline, Month 6
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to Month 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Medical Responsible study director
Merck Ltd.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bisoprolol in people with Hypertension and Diabetes Mellitus, Type II, run by Merck KGaA, Darmstadt, Germany at 1 site in South Korea.
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 14 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: finished, as of the sponsor's last update on 4 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Month 6 (time frame: Baseline, Month 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Jul 2014.