To Compare the Safety and Efficacy of Dapagliflozin Plus Metformin Versus Sitagliptin Plus Metformin for Treatment of Diabetes in Patients With Compensated and Stable Decompensated Cirrhosis

Decompensated Cirrhosis Clinical Trial

Official title:

An Open Label Randomized Control Trial to Compare the Safety and Efficacy of Dapagliflozin Plus Metformin Versus Sitagliptin Plus Metformin for Treatment of Diabetes in Patients With Compensated and Stable Decompensated Cirrhosis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06147518
• Other study ID #: ILBS-Cirrhosis-68
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 20, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: November 2023
• Source: Institute of Liver and Biliary Sciences, India
• Contact: Dr Jayashree Biswas, MD
• Phone: 01146300000
• Email: jayashreeb790[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Diabetes prevalence is increasing among cirrhotics and use of OAD in cirrhotics is limited because of risk of hypoglycaemia and other adverse effects, therefore in this study we would be using OAD in the form of Sitagliptin or Dapagliflozin to look for glycemic response as well as to look for other benefits such as weight reduction and improvement in lipid parameters.

Description:

Hypothesis In patients with cirrhosis and T2DM with poor glycemic control on metformin requiring dual therapy, Dapagliflozin is safe and superior to Sitagliptin in achieving glycemic control. Moreover, Dapagliflozin use leads to improvement in parameters of metabolic dysfunction, clinical decompensation and cardio-renal protection.

Aim compare the safety and efficacy of metformin plus sitagliptin compared to metformin plus dapagliflozin in effective glycemic control and improvement in parameters of metabolic dysfunction, cirrhosis complications and organ dysfunction at 24 weeks.

Study population:Patients with compensated and stable decompensated cirrhosis and age 18-70 years with CTP 5-8

Study design: A prospective, randomized, single center open label study

The study will be conducted on the consecutive patients with liver cirrhosis and type 2 diabetes mellitus seen at the outpatient clinics of Department of Hepatology, ILBS

Sample size: 200 Assuming that 40% people had HbA1c <7 in Dapagliflozin and 25% in sitagliptin.Alpha = 5%,Power = 80%,Need to enroll total 200 cases(100 in each arm), Drop rate = 10%,Total enrollment = 100 cases (80 each arm).

Randomization by block randomization method taking block size as 10 Intervention: This RCT will be conducted at ILBS New Delhi

Monitoring and assessment: Monitoring will be done for all the parameters of the objective. Documentation will be done for any adverse effects which will happen.

Adverse effects: to be monitored

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 240
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Age 18-70 years

2. Child A/B Liver cirrhosis in outpatient setting

3. T2DM patients who have not used any glucose-lowering agents within 8 weeks before consenting, or those who have only used metformin, in addition to diet and exercise

4. HbA1c level of 7.1% or higher but no more than 9.0%

5. BMI of 23 kg/m2 or higher

6. patients who can be monitored closely for medication compliance

7. patients who provide written informed consent.

Exclusion Criteria:

1. Age <18 years

2. Post renal or liver transplantation

3. CTP C / ACLF

4. Intrinsic/structural kidney disease, obstructive uropathy, ADPKD, Anatomic urologic defects that predispose to urinary tract infection

5. Active sepsis / SBP at enrollment

6. Grade II/III/IV HE

7. Pregnancy or Lactating mother

8. Known CKD, obstructive uropathy

9. Patient on MV, NIV, systemic sepsis and shock

10. Lack of informed consent

11. Prior intolerance or S/E to SGLT-2i or DPP4i

12. patients with type 1 diabetes or secondary diabetes

13. patients with medical history of diabetic ketoacidosis

14. patients with medical history of myocardial infarction, cerebral infarction, or stroke within 12 weeks before consent to the study

15. estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m2

16. unstable hypertension or dyslipidemia within 12 weeks before consent to the study

17. HB <9 g/L, patients with haemoglobinopathy, acute hemolysisStudy period: one year after ethical approval.

Related Conditions & MeSH terms

• Compensated Cirrhosis
• Decompensated Cirrhosis
• Fibrosis
• Liver Cirrhosis

Intervention

Drug:
• Metformin
Metformin: 1.5g/d CTPA,1g/d CTPB
• Sitagliptin
Sitagliptin: Assess HbA1c/HBSG at 8 weeks, increase sitagliptin to 100 mg if HbA1c>7%
• Dapagliflozin
Assess HbA1c/HBSG at 8 weeks, increase Dapagliflozin to 10 mg if HbA1c>7%

Locations

Country	Name	City	State
India	Dr Rakesh Kumar Jagdish	New Delhi	Delhi

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Liver and Biliary Sciences, India

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with glycemic control at 24 weeks (HBA1c <7.0 %)		24 weeks
Secondary	Percentage of patients with glycemic control at 8 and 16 weeks (HBA1c <7.0 %)		8 and 16 weeks
Secondary	Ideal body weight loss of =3% relative to baseline at 24 week		24 weeks
Secondary	Incidence and frequency of hypoglycemia (BS <54 mg/dl) episodes		8 weeks
Secondary	Incidence and frequency of hypoglycemia (BS <54 mg/dl) episodes		16 weeks
Secondary	Incidence and frequency of hypoglycemia (BS <54 mg/dl) episodes		24 weeks
Secondary	Changes in HbA1c at 24 week relative to baseline		24 weeks
Secondary	Changes in BMI at 24 week relative to baseline		24 weeks
Secondary	changes in Blood insulin at 24 week		24 weeks
Secondary	changes in lipid profile at 24 week		24 weeks
Secondary	Change in ALT at 8, 16 and 24 week		8, 16 and 24 week
Secondary	Change in HVPG at 24 week compared to baseline		24 weeks
Secondary	Change in LSM at 24 week compared to baseline		24 weeks
Secondary	Change in SSM at 24 week compared to baseline		24 weeks
Secondary	Incidence of urinary protein excretion at 8, 16 and 24 weeks		8, 16 and 24 weeks
Secondary	Incidence of serum creatinine at 8, 16 and 24 weeks		8, 16 and 24 weeks
Secondary	Number of patients with Complications of cirrhosis (ascites, HE, Bleed, AKI, Infection) at 24 week		24 weeks
Secondary	Medicine adherence rate in both groups		24 weeks
Secondary	Adverse effects to study drugs in both groups		24 weeks
Secondary	Number of patients with Mortality/ Liver transplantation in both groups		24 weeks