search
Back to results

Empagliflozin and ACEi- Effects on Hyperfiltration: BETWEEN Study

Primary Purpose

Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Obesity

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Empagliflozin
Placebo (matching empagliflozin)
ramipril
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Signed and dated written informed consent.
  • Male or female patients diagnosed with type 1 diabetes (T1D) at least 6 months prior to informed consent or type 2 diabetes (T2D) or non-diabetic obese patients.
  • T1D patients must use and be willing of and be willing to continue throughout the duration of the trial either:
  • multiple daily injections of insulin OR
  • continuous sub-cutaneous insulin infusion of any insulin type, with at least 3 months experience
  • For patients with T1D or T2D,HbA1c of 6.5 - 11%
  • Age at least 18 years of age
  • Body mass index of >=18.5 kg/m^2
  • Estimated glomerular filtration rate greater than or equal to 60 ml/min/1.73m2
  • Blood pressure greater than 90 /60 mmHg and less than or equal to 140 / 90 mmHg
  • Use of a highly effective method of contraception.
  • Further inclusion criteria apply

Exclusion criteria:

  • For patients with T1D, treatment with an antihyperglycaemic agent within 3 months prior to visit 1
  • occurrence of severe hypoglycaemia within 3 months prior to visit 1
  • hypoglycaemic unawareness within 3 months prior to visit 1
  • occurrence of diabetic ketoacidosis within 3 months of visit 1 and until visit 3 Further exclusion criteria apply

Sites / Locations

  • Toronto General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Sequence A

Sequence B

Arm Description

Empagliflozin followed by a wash-out followed by empagliflozin matching placebo on a background of open label ramipril.

Empagliflozin matching placebo followed a wash-out followed by empagliflozin on a background of open label ramipril.

Outcomes

Primary Outcome Measures

Glomerular Filtration Rate (GFR) Under Euglycaemic Conditions After 4 Weeks of Treatment With Either Empagliflozin Added to Ramipril or Placebo Added to Ramipril.
Glomerular filtration rate (GFR) under euglycaemic conditions after 4 weeks of treatment with either empagliflozin added to ramipril or placebo added to ramipril. The pre-specified statistical analysis was not conducted, because data are too sparse in the subgroup of hyperfilterers.

Secondary Outcome Measures

Filtration Status (Glomerular Filtration Rate (GFR) < 120 mL/Min/1.73m², Yes/no) After 4 Weeks of Treatment With Either Empagliflozin Added to Ramipril or Placebo Added to Ramipril
Filtration status (Glomerular Filtration Rate (GFR) < 120 mL/min/1.73m²) after 4 weeks of treatment with either empagliflozin added to ramipril or placebo added to ramipril. Filtration status is defined as whether a patient has normal Filtration status (GFR < mL/min/1.73m², "yes") or not (GFR ≥ mL/min/1.73m², "no"). The pre-specified statistical analysis was not conducted, because data are too sparse in the subgroup of hyperfilterers.

Full Information

First Posted
December 15, 2015
Last Updated
July 23, 2020
Sponsor
Boehringer Ingelheim
Collaborators
Eli Lilly and Company
search

1. Study Identification

Unique Protocol Identification Number
NCT02632747
Brief Title
Empagliflozin and ACEi- Effects on Hyperfiltration: BETWEEN Study
Official Title
A Double-blind, Placebo Controlled, Cross-over Renal Mechanistic Trial to Assess the Effect of Adding Empagliflozin Versus Placebo on Renal Hyperfiltration on a Background of the Angiotensin Converting Enzyme Inhibitor (ACEi) Ramipril: BETWEEN Study
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
May 10, 2016 (Actual)
Primary Completion Date
December 19, 2017 (Actual)
Study Completion Date
July 2, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
Collaborators
Eli Lilly and Company

4. Oversight

5. Study Description

Brief Summary
This is a randomized, double-blind, double-dummy, placebo-controlled, cross over design trial with empagliflozin compared to placebo that is added to open-label ramipril.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Obesity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sequence A
Arm Type
Experimental
Arm Description
Empagliflozin followed by a wash-out followed by empagliflozin matching placebo on a background of open label ramipril.
Arm Title
Sequence B
Arm Type
Experimental
Arm Description
Empagliflozin matching placebo followed a wash-out followed by empagliflozin on a background of open label ramipril.
Intervention Type
Drug
Intervention Name(s)
Empagliflozin
Intervention Description
Empagliflozin will be taken once daily
Intervention Type
Drug
Intervention Name(s)
Placebo (matching empagliflozin)
Intervention Description
Placebo will be taken once daily
Intervention Type
Drug
Intervention Name(s)
ramipril
Intervention Description
Ramipril will be taken once or twice daily
Primary Outcome Measure Information:
Title
Glomerular Filtration Rate (GFR) Under Euglycaemic Conditions After 4 Weeks of Treatment With Either Empagliflozin Added to Ramipril or Placebo Added to Ramipril.
Description
Glomerular filtration rate (GFR) under euglycaemic conditions after 4 weeks of treatment with either empagliflozin added to ramipril or placebo added to ramipril. The pre-specified statistical analysis was not conducted, because data are too sparse in the subgroup of hyperfilterers.
Time Frame
At week 4 and at week 12
Secondary Outcome Measure Information:
Title
Filtration Status (Glomerular Filtration Rate (GFR) < 120 mL/Min/1.73m², Yes/no) After 4 Weeks of Treatment With Either Empagliflozin Added to Ramipril or Placebo Added to Ramipril
Description
Filtration status (Glomerular Filtration Rate (GFR) < 120 mL/min/1.73m²) after 4 weeks of treatment with either empagliflozin added to ramipril or placebo added to ramipril. Filtration status is defined as whether a patient has normal Filtration status (GFR < mL/min/1.73m², "yes") or not (GFR ≥ mL/min/1.73m², "no"). The pre-specified statistical analysis was not conducted, because data are too sparse in the subgroup of hyperfilterers.
Time Frame
At week 4 and at week 12.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Signed and dated written informed consent. Male or female patients diagnosed with type 1 diabetes (T1D) at least 6 months prior to informed consent or type 2 diabetes (T2D) or non-diabetic obese patients. T1D patients must use and be willing of and be willing to continue throughout the duration of the trial either: multiple daily injections of insulin OR continuous sub-cutaneous insulin infusion of any insulin type, with at least 3 months experience For patients with T1D or T2D,HbA1c of 6.5 - 11% Age at least 18 years of age Body mass index of >=18.5 kg/m^2 Estimated glomerular filtration rate greater than or equal to 60 ml/min/1.73m2 Blood pressure greater than 90 /60 mmHg and less than or equal to 140 / 90 mmHg Use of a highly effective method of contraception. Further inclusion criteria apply Exclusion criteria: For patients with T1D, treatment with an antihyperglycaemic agent within 3 months prior to visit 1 occurrence of severe hypoglycaemia within 3 months prior to visit 1 hypoglycaemic unawareness within 3 months prior to visit 1 occurrence of diabetic ketoacidosis within 3 months of visit 1 and until visit 3 Further exclusion criteria apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
35862082
Citation
Lytvyn Y, Kimura K, Peter N, Lai V, Tse J, Cham L, Perkins BA, Soleymanlou N, Cherney DZI. Renal and Vascular Effects of Combined SGLT2 and Angiotensin-Converting Enzyme Inhibition. Circulation. 2022 Aug 9;146(6):450-462. doi: 10.1161/CIRCULATIONAHA.122.059150. Epub 2022 Jul 11.
Results Reference
derived
Links:
URL
https://trials.boehringer-ingelheim.com
Description
Related Info

Learn more about this trial

Empagliflozin and ACEi- Effects on Hyperfiltration: BETWEEN Study

We'll reach out to this number within 24 hrs