Type 2 Diabetes MellitusPhase 4NCT04013581
Quadruple Oral Combination Therapy for Type 2 Diabetes Mellitus : Glycemic Control by Thiazolidinedione (TZD) or Sodium Glucose Co-transporter 2 (SGLT-2) Inhibitor as an add-on Therapy in Type 2 Diabetes Mellitus After Failure of an Oral Triple Antidiabetic Regimen
A Phase 4 study testing TZD group and SGLT-2 group in people with Type 2 Diabetes Mellitus, run by Yonsei University at 1 site in South Korea.
Trial summary
In the treatment of type 2 diabetes (T2D), the number of patients requiring combination therapy of oral antidiabetic agents (OADs) is more than 70%. Especially in Korea, the tendency to avoid insulin therapy is relatively higher than other countries, therefore, the need for combination therapy of OADs is quite high. Read more about this study
- Who is it for?
- Ages 19 to 80 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- TZD group and SGLT-2 group
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 121 participants
- Where
- 1 siteSouth Korea
- Study dates
- 5 Aug 2019to 28 May 2020
- Phase
- Phase 4
- 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 19 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. 19 ≤ age ≤ 80, male or female
- 2. Type 2 diabetes patients who have taken triple combination therapy of OADs as followed : Metformin (≥1000 mg/day), Sulfonylurea (Glimepiride ≥ 4 mg/day or Gliclazide ≥ 60 mg/day), DPP-4 inhibitor (Full dose) for over 12 weeks
- 3. At screening, 7% < HbA1c ≤ 10%
- 4. Patients who refused insulin therapy.
- 5. Subjects who understood the contents of the clinical trial and are cooperative in the trial progress, and are considered to be able to participate until the end of the trial.
- 6. Patients who have voluntarily agreed in writing to participate in the clinical trial after hearing the explanation of the trial.
Who cannot join
- 1. Type 1 diabetes, gestational diabetes, and other types of diabetes than type 2 diabetes mellitus.
- 2. Patients who have the history of allergy of hypersensitivity for the medication of the clinical trial.
- 3. Patients who have the history of taking TZDs or SGLT-2 inhibitors within a year prior to screening visit, or have the history of discontinuation of them due to severe side effects.
- 4. Patients who have the history of acute or chronic metabolic acidosis including diabetic ketoacidosis (with or without coma), or any kinds of ketosis within 12 weeks prior to screening visit.
- 5. Patients who have genetic metabolic diseases, such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
- 6. Patients who have the history of taking steroids for more than 2 weeks, within 8 weeks prior to screening visit.
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- 7. Patients who have the history of malignancy within 5 years prior to screening visit (In case of bladder cancer, subjects will be excluded regardless of the time of diagnosis)
- 8. Patients who have the history of coronary artery bypass surgery or percutaneous coronary intervention, or suffered from heart failure (NYHA class III, IV)
- 9. Patients who have the history of uncontrolled arrhythmia, unstable angina, myocardial infarction, stroke, transient ischemic attacks, and cerebral vascular disease within 24 weeks prior to the screening date.
- 10. Patients of chronic renal failure, chronic kidney disease stage 3~5 (estimated glomerular filtration rate calculated vial CKD-EPI <60 mL/min/1.73m2) or on dialysis therapy.
- 11. Elevated liver enzymes (AST, ALT, ALP ≥ 2.5*upper limit of normal (ULN) or Total bilirubin ≥ 2.5*ULN) or Child-Pugh class B or C (for the patients of liver cirrhosis)
- 12. Subjects who are pregnant or lactating
- 13. Perioperative patients, patients with severe infections or severe trauma
- 14. Patients with unexamined gross hematuria
- 15. Any other subjects who is determined to be ineligible for the clinical trials by researchers.
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine
Seoul
About this study
In the treatment of type 2 diabetes (T2D), the number of patients requiring combination therapy of oral antidiabetic agents (OADs) is more than 70%. Especially in Korea, the tendency to avoid insulin therapy is relatively higher than other countries, therefore, the need for combination therapy of OADs is quite high. However, according to the current guidelines, clinicians are recommended to prescribe three or fewer OADs as the combination therapy for T2D. Recently, various OADs have been developed, and it is expected that quadruple combination therapy of OADs would be quite effective to lower blood glucose levels. In the present study, the investigators designed the study to compare the efficacy and safety of quadruple combination therapy; thiazolidinedione (TZD) vs. SGLT-2 inhibitor as an add-on therapy to triple combination therapy (Metformin, Sulfonylurea, Dipeptidyl peptidase-4(DPP-4) inhibitors). Quadruple combination therapy group with the SGLT-2 inhibitor will be considered as active control group, because it have shown non-inferior glycemic efficacy to the conventional insulin conversion therapy in a previous clinical study. Patients who could not achieve the target blood glucose level (7% <HbA1c ≤ 10%) under the triple combination therapy (Metformin, Sulfonylurea, DPP-4 inhibitors) for more than 12 weeks will be enrolled in this prospective, open-label, randomized, parallel comparison, multicenter clinical trial. Subjects in each group (60 patients/group) will be treated with TZD-containing quadruple therapy or SGLT-2 inhibitor-containing quadruple therapy for 24 weeks. The investigators will evaluate the glycemic efficacy and safety of each group. Primary outcome is the 24 week-change of HbA1c from baseline levels.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- TZD group, SGLT-2 group
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TZD groupDrug
Also called Acpio
Pioglitazone 15mg (Acpio®, once daily, regardless of meal time, for 24 weeks) will be added for T2DM(type 2 diabetes mellitus) patients who had inadequate glycemic control (7% <HbA1c ≤ 10%) with triple therapy (metformin, DPP-4 inhibitors, sulfonylurea). At visit 3 (after 12 week-treatment), patients whose HbA1c level is more than 7.0% will be prescribed increased dosage of pioglitazone : from 15mg to 30mg
SGLT-2 groupDrug
Also called Jardiance
Empagliflozin 10mg (Jardiance®, once daily, regardless of meal time, for 24 weeks) will be added for T2DM patients who had inadequate glycemic control (7% <HbA1c ≤ 10%) with triple therapy (metformin, DPP-4 inhibitors, sulfonylurea). At visit 3 (after 12 week-treatment), patients whose HbA1c level is more than 7.0% will be prescribed increased dosage of empagliflozin : from 10mg to 25mg
| Study group | Role | What they receive |
|---|---|---|
| TZD group | Experimental | Pioglitazone added to Metformin, DPP-4 inhibitors, Sulfonylurea Receives: Drug: TZD group |
| SGLT-2 inhibitor group | Active comparator | Empagliflozin added to Metformin, DPP-4 inhibitors, Sulfonylurea Receives: Drug: SGLT-2 group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of HbA1c
Measured: 12 weeks
Change of HbA1c
Mean difference of HbA1c after 24 week-treatment
Measured: 24 weeks
Secondary outcomes (12)
glucose
Percentage of patients who achieve target HbA1c (≤7% level)
Measured: 12 weeks
glucose
Mean difference of fasting blood glucose after 24 week-treatment
Measured: 24 weeks
Adverse events
Incidence of adverse events during treatment period
Measured: 12 weeks
Adverse events
Incidence of adverse events during treatment period
Measured: 24 weeks
Change of kidney function
Mean change of BUN and serum creatinine
Measured: 12 weeks
Change of kidney function
Mean change of BUN and serum creatinine
Measured: 24 weeks
Change of liver enzymes
Mean change of AST(Asparate aminotransferase)
Measured: 12 weeks
Change of liver enzymes
Mean change of ALT(Alanine aminotransferase)
Measured: 12 weeks
Change of liver enzymes
Mean change of Total bilirubin
Measured: 12 weeks
Change of liver enzymes
Mean change of AST
Measured: 24 weeks
Change of liver enzymes
Mean change of ALT
Measured: 24 weeks
Change of liver enzymes
Mean change of Total bilirubin
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2019
- Study start5 Aug 2019
- Primary completion13 May 2020
- Study completion28 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, open label, randomized, parallel, multicenter clinical trial
- Masking
- None (open label)
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04013581
- Sponsor's protocol ID
- 4-2019-0393
- Status last verified
- May 2021
- First submitted
- 2 Jul 2019
- Last updated
- 4 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quadruple Oral Combination Therapy for Type 2 Diabetes Mellitus : Glycemic Control by Thiazolidinedione (TZD) or Sodium Glucose Co-transporter 2 (SGLT-2) Inhibitor as an add-on Therapy in Type 2 Diabetes Mellitus After Failure of an Oral Triple Antidiabetic Regimen
- ClinicalTrials.gov ID
- NCT04013581
- Acronym / sponsor ID
- 4-2019-0393
- Conditions
- Type 2 Diabetes Mellitus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 5 Aug 2019 (actual)
- Primary completion
- 13 May 2020 (actual)
- Study completion
- 28 May 2020 (actual)
- First posted
- 9 Jul 2019 (actual)
- 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.
In the treatment of type 2 diabetes (T2D), the number of patients requiring combination therapy of oral antidiabetic agents (OADs) is more than 70%. Especially in Korea, the tendency to avoid insulin therapy is relatively higher than other countries, therefore, the need for combination therapy of OADs is quite high. However, according to the current guidelines, clinicians are recommended to prescribe three or fewer OADs as the combination therapy for T2D. Recently, various OADs have been developed, and it is expected that quadruple combination therapy of OADs would be quite effective to lower blood glucose levels. In the present study, the investigators designed the study to compare the efficacy and safety of quadruple combination therapy; thiazolidinedione (TZD) vs. SGLT-2 inhibitor as an add-on therapy to triple combination therapy (Metformin, Sulfonylurea, Dipeptidyl peptidase-4(DPP-4) inhibitors). Quadruple combination therapy group with the SGLT-2 inhibitor will be considered as active control group, because it have shown non-inferior glycemic efficacy to the conventional insulin conversion therapy in a previous clinical study. Patients who could not achieve the target blood glucose level (7% <HbA1c ≤ 10%) under the triple combination therapy (Metformin, Sulfonylurea, DPP-4 inhibitors) for more than 12 weeks will be enrolled in this prospective, open-label, randomized, parallel comparison, multicenter clinical trial. Subjects in each group (60 patients/group) will be treated with TZD-containing quadruple therapy or SGLT-2 inhibitor-containing quadruple therapy for 24 weeks. The investigators will evaluate the glycemic efficacy and safety of each group. Primary outcome is the 24 week-change of HbA1c from baseline levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective, open label, randomized, parallel, multicenter clinical trial
| Arm | Type | Receives |
|---|---|---|
| TZD group | Experimental | Drug: TZD groupPioglitazone added to Metformin, DPP-4 inhibitors, Sulfonylurea |
| SGLT-2 inhibitor group | Active comparator | Drug: SGLT-2 groupEmpagliflozin added to Metformin, DPP-4 inhibitors, Sulfonylurea |
Who may qualify
- Ages
- 19 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 1. 19 ≤ age ≤ 80, male or female
- 2. Type 2 diabetes patients who have taken triple combination therapy of OADs as followed : Metformin (≥1000 mg/day), Sulfonylurea (Glimepiride ≥ 4 mg/day or Gliclazide ≥ 60 mg/day), DPP-4 inhibitor (Full dose) for over 12 weeks
- 3. At screening, 7% < HbA1c ≤ 10%
- 4. Patients who refused insulin therapy.
- 5. Subjects who understood the contents of the clinical trial and are cooperative in the trial progress, and are considered to be able to participate until the end of the trial.
Key exclusion criteria (15 listed)
- 1. Type 1 diabetes, gestational diabetes, and other types of diabetes than type 2 diabetes mellitus.
- 2. Patients who have the history of allergy of hypersensitivity for the medication of the clinical trial.
- 3. Patients who have the history of taking TZDs or SGLT-2 inhibitors within a year prior to screening visit, or have the history of discontinuation of them due to severe side effects.
- 4. Patients who have the history of acute or chronic metabolic acidosis including diabetic ketoacidosis (with or without coma), or any kinds of ketosis within 12 weeks prior to screening visit.
- 5. Patients who have genetic metabolic diseases, such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
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 |
|---|---|---|
| TZD groupAlso: AcpioPioglitazone 15mg (Acpio®, once daily, regardless of meal time, for 24 weeks) will be added for T2DM(type 2 diabetes mellitus) patients who had inadequate glycemic control (7% <HbA1c ≤ 10%) with triple therapy (metformin, DPP-4 inhibitors, sulfonylurea). At visit 3 (after 12 week-treatment), patients whose HbA1c level is more than 7.0% will be prescribed increased dosage of pioglitazone : from 15mg to 30mg | Drug | TZD group |
| SGLT-2 groupAlso: JardianceEmpagliflozin 10mg (Jardiance®, once daily, regardless of meal time, for 24 weeks) will be added for T2DM patients who had inadequate glycemic control (7% <HbA1c ≤ 10%) with triple therapy (metformin, DPP-4 inhibitors, sulfonylurea). At visit 3 (after 12 week-treatment), patients whose HbA1c level is more than 7.0% will be prescribed increased dosage of empagliflozin : from 10mg to 25mg | Drug | SGLT-2 inhibitor group |
Primary outcome
Change of HbA1c
Time frame: 12 weeks
Change of HbA1c
Time frame: 24 weeks
Mean difference of HbA1c after 24 week-treatment
12 secondary outcomes
glucose
Time frame: 12 weeks
glucose
Time frame: 24 weeks
Adverse events
Time frame: 12 weeks
Adverse events
Time frame: 24 weeks
Change of kidney function
Time frame: 12 weeks
Change of kidney function
Time frame: 24 weeks
Change of liver enzymes
Time frame: 12 weeks
Change of liver enzymes
Time frame: 12 weeks
Change of liver enzymes
Time frame: 12 weeks
Change of liver enzymes
Time frame: 24 weeks
Change of liver enzymes
Time frame: 24 weeks
Change of liver enzymes
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2021.
- Individual participant dataSharing planned: No
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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 record lists no contact. Use the official record to reach the sponsor.
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 TZD group and SGLT-2 group in people with Type 2 Diabetes Mellitus, run by Yonsei University 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 6 inclusion and 15 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 May 2021. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 of HbA1c (time frame: 12 weeks). The study lists 2 primary outcomes in all. 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 May 2021.