Chronic Kidney DiseasesPhase 2ADAPTNCT04794517
Dapagliflozin in Non-diabetic Stage IV CKD
A Phase 2 study testing Dapagliflozin 10Mg Tab in people with Chronic Kidney Diseases, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
Trial summary
This is a phase 2b, prospective, randomized, cross-over, double-blind, placebo-controlled trial primarily aimed at assessing whether the SGLT2 inhibitor dapagliflozin ameliorates hyperfiltration and reduces proteinuria as compared to placebo in patients with non-diabetic CKD, with particular focus on those at highest… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Kidney Diseases
- What is being tested?
- Dapagliflozin 10Mg Tab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteItaly
- Study dates
- 8 Nov 2021to 7 May 2024
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent prior to any study specific procedures
- Male or female more than 18 year old
- Non-diabetic Stage-IV CKD
- Fasting blood glucose ≤ 125 mg (≤ 6.9 mmol/l) and HbA1C ≤6.4% (≤ 47 mmol/mol)58 without treatment with oral blood glucose lowering medications and/or insulin
- Two-hour plasma glucose <200 mg/dl during 75-g oral glucose tolerance test (OGTT)58
- Persistent proteinuria (24-hour urinary protein excretion ≥ 0.5 grams in at least two consecutive evaluations >1 week apart) despite RAS inhibitor therapy with ACE inhibitors and/or ARBs (or without RAS inhibitors in patients with specific contraindications to these medications)
Show all 12Show fewer
- eGFR 15 to 30 ml/min/1.73 m2 by CKD-Epi equation
- Blood pressure <150/90 mmHg without changes in blood pressure lowering medications over the last four weeks before the randomization
- Negative pregnancy test (urine or serum) for female subjects of childbearing potential.10
- Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of dapagliflozin\placebo to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.
- Male subjects must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of IMP to prevent pregnancy in a partner.
- Subjects who are blood donors should not donate blood during the study and for 3 months following their last dose of dapagliflozin\placebo.
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
- Participation in another clinical study with an investigational product during the last month
- Ischemic kidney disease (because of possible excess risk of acute kidney injury upon SGLT2-inhibitor associated reduction in sodium pool and kidney perfusion pressure)
- Rapidly progressive kidney disease (e GFR reduction ≥ 30% over the last three months) and expected risk of progression to end stage kidney failure and need of renal replacement therapy by dialysis or transplantation during the study period.
- Active systemic autoimmune diseases;
- Concomitant treatment with steroids or any other immunosuppressive agent
Show all 16Show fewer
- Hypersensitivity to the active principle (dapagliflozin) or any of the excipients (e.g. lactose);
- Severe/unstable heart failure with or without decreased systolic function requiring hospitalization or changes in pharmacological therapy over the last three months
- Uncontrolled hypertension (BP >150/90 mmHg despite optimized pharmacological treatment and diet or symptomatic hypotension
- Positive hepatitis C antibody hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening
- Known to have tested positive for human immunodeficiency virus
- Drug or alcohol abuse
- Inability to fully understand the possible risks and benefits related to study participation
- If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 90 days after last dose; or intending to donate ova during such time period;
- If male, the subject intends to donate sperm while on the study this study or for 90 days after last dose;
- Participation in another interventional clinical trial within the 4 weeks prior to screening.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò"
Ranica, BG, 24020
About this study
Official title: Evaluating the Short-term Renal and Systemic Effects of Dapagliflozin in Non-diabetic Patients With Stage IV CKD at Risk of ESKD Because of Severe Renal Insufficiency and Persistent Proteinuria
This is a phase 2b, prospective, randomized, cross-over, double-blind, placebo-controlled trial primarily aimed at assessing whether the SGLT2 inhibitor dapagliflozin ameliorates hyperfiltration and reduces proteinuria as compared to placebo in patients with non-diabetic CKD, with particular focus on those at highest risk of progression to end stage kidney disease (ESKD) because of severe renal insufficiency (Stage IV CKD) and proteinuria (>0.5 g/24 hours). The study will also evaluate renal and systemic mechanisms mediating treatment effects on GFR and will explore biochemical factors possibly mediating these effects.
Read the detailed description
As chronic kidney disease (CKD) continues to increase worldwide, along with the demand for related life-saving therapies, the financial burden of CKD will place an increasing drain on health care systems. Experimental studies showed that glomerular capillary hypertension and impaired sieving function with consequent protein overload play a pathogenic role in the progression of CKD. Consistently, human studies show that proteinuria is an independent predictor of progression and that its reduction is renoprotective. At comparable BP control, inhibitors of the renin-angiotensin system (RAS), including angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), more effectively than non-RAS inhibitor therapy reduce proteinuria, slow progression to ESRD, and even improve the kidney function achieving disease regression in some cases. In participants with diabetes, RAS inhibitors delay the onset of microalbuminuria and its progression to macroalbuminuria, and ACE inhibitors may reduce the excess cardiovascular mortality associated with diabetic renal disease. In addition to RAS inhibitors, however, multimodal approaches including lifestyle modifications and multidrug therapy will be required in most cases to optimize control of the several risk factors for CKD and related cardiovascular morbidity. Novel medications, including proximal tubular sodium - glucose co-transporter -2 (SGLT2 inhibitors - that ameliorate glomerular hyperfiltration and proteinuria and slow renal disease progression in type 2 diabetes by mechanisms apparently independent of improved metabolic control - might help further improve the cost-effectiveness of renoprotective interventions even in non-diabetic CKD. This phase 2, prospective, randomized, cross over, placebo-controlled trial will primarily aim to assess whether the SGLT2 inhibitor dapagliflozin ameliorates hyperfiltration and reduces proteinuria as compared to placebo in patients with non-diabetic CKD, with particular focus on those at highest risk of progression to end stage kidney disease (ESKD) because of severe renal insufficiency (Stage IV CKD) and proteinuria (>0.5 g/24 hours).
- Conditions
- Chronic Kidney Diseases
- Being tested
- Dapagliflozin 10Mg Tab, Placebo
- Keywords
- Chronic kidney disease, Proteinuria, Dapagliflozin
- Medical subject headings
- Renal Insufficiency, Chronic, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin 10Mg TabDrug
Dapagliflozin 10 mg/die will be administered orally for six-weeks.
PlaceboOther
Placebo one tablet/die will be administered orally for six-weeks.
| Study group | Role | What they receive |
|---|---|---|
| IMP | Experimental | Dapagliflozin 10 mg/die will be administered orally for six-weeks. Receives: Drug: Dapagliflozin 10Mg Tab |
| Placebo | Placebo comparator | Placebo, one tablet/die will be administered orally for six-weeks. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glomerular Filtration rate (GFR)
GFR measured by the Iohexol plasma clearance technique
Measured: Changes from baseline and day 1, 8, 42,84, 92,126 and 140.
24-hour urinary protein excretion
24-hour urinary protein excretion will be measured as median of three measurements in three consecutive 24-hour urine collections
Measured: Changes from start (day 0, day 84) and end (day 42, day 126) of each Treatment Period with dapagliflozin or placebo
Secondary outcomes (1)
Renal plasma flow (RPF)
RPF will be assessed by the Para Amino Hippuric (PAH) plasma clearance technique.
Measured: Changes from baseline and day 1, 8, 42,84, 92,126 and 140.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2021
- Study start8 Nov 2021
- Primary completion7 May 2024
- Study completion7 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney DiseasesStudies of the same condition, open and under way.
- More trials run by Mario Negri Institute for Pharmacological ResearchThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Giuseppe Remuzzi, MD, Study director, Istituto Di Ricerche Farmacologiche Mario Negri
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04794517
- Sponsor's protocol ID
- ADAPT
- Other IDs
- 2021-000726-10
- Acronym
- ADAPT
- Status last verified
- May 2024
- First submitted
- 8 Mar 2021
- Last updated
- 10 May 2024
- 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 10 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Short-term Renal and Systemic Effects of Dapagliflozin in Non-diabetic Patients With Stage IV CKD at Risk of ESKD Because of Severe Renal Insufficiency and Persistent Proteinuria
- ClinicalTrials.gov ID
- NCT04794517
- Acronym / sponsor ID
- ADAPT / ADAPT
- Conditions
- Chronic Kidney Diseases
- Keywords
- Chronic kidney disease, Proteinuria, Dapagliflozin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 8 Nov 2021 (actual)
- Primary completion
- 7 May 2024 (actual)
- Study completion
- 7 May 2024 (actual)
- First posted
- 12 Mar 2021 (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.
This is a phase 2b, prospective, randomized, cross-over, double-blind, placebo-controlled trial primarily aimed at assessing whether the SGLT2 inhibitor dapagliflozin ameliorates hyperfiltration and reduces proteinuria as compared to placebo in patients with non-diabetic CKD, with particular focus on those at highest risk of progression to end stage kidney disease (ESKD) because of severe renal insufficiency (Stage IV CKD) and proteinuria (>0.5 g/24 hours). The study will also evaluate renal and systemic mechanisms mediating treatment effects on GFR and will explore biochemical factors possibly mediating these effects.
Detailed description
As chronic kidney disease (CKD) continues to increase worldwide, along with the demand for related life-saving therapies, the financial burden of CKD will place an increasing drain on health care systems. Experimental studies showed that glomerular capillary hypertension and impaired sieving function with consequent protein overload play a pathogenic role in the progression of CKD. Consistently, human studies show that proteinuria is an independent predictor of progression and that its reduction is renoprotective. At comparable BP control, inhibitors of the renin-angiotensin system (RAS), including angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), more effectively than non-RAS inhibitor therapy reduce proteinuria, slow progression to ESRD, and even improve the kidney function achieving disease regression in some cases. In participants with diabetes, RAS inhibitors delay the onset of microalbuminuria and its progression to macroalbuminuria, and ACE inhibitors may reduce the excess cardiovascular mortality associated with diabetic renal disease. In addition to RAS inhibitors, however, multimodal approaches including lifestyle modifications and multidrug therapy will be required in most cases to optimize control of the several risk factors for CKD and related cardiovascular morbidity. Novel medications, including proximal tubular sodium - glucose co-transporter -2 (SGLT2 inhibitors - that ameliorate glomerular hyperfiltration and proteinuria and slow renal disease progression in type 2 diabetes by mechanisms apparently independent of improved metabolic control - might help further improve the cost-effectiveness of renoprotective interventions even in non-diabetic CKD. This phase 2, prospective, randomized, cross over, placebo-controlled trial will primarily aim to assess whether the SGLT2 inhibitor dapagliflozin ameliorates hyperfiltration and reduces proteinuria as compared to placebo in patients with non-diabetic CKD, with particular focus on those at highest risk of progression to end stage kidney disease (ESKD) because of severe renal insufficiency (Stage IV CKD) and proteinuria (>0.5 g/24 hours).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IMP | Experimental | Drug: Dapagliflozin 10Mg TabDapagliflozin 10 mg/die will be administered orally for six-weeks. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo, one tablet/die will be administered orally for six-weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Provision of informed consent prior to any study specific procedures
- Male or female more than 18 year old
- Non-diabetic Stage-IV CKD
- Fasting blood glucose ≤ 125 mg (≤ 6.9 mmol/l) and HbA1C ≤6.4% (≤ 47 mmol/mol)58 without treatment with oral blood glucose lowering medications and/or insulin
- Two-hour plasma glucose <200 mg/dl during 75-g oral glucose tolerance test (OGTT)58
Key exclusion criteria (16 listed)
- Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
- Participation in another clinical study with an investigational product during the last month
- Ischemic kidney disease (because of possible excess risk of acute kidney injury upon SGLT2-inhibitor associated reduction in sodium pool and kidney perfusion pressure)
- Rapidly progressive kidney disease (e GFR reduction ≥ 30% over the last three months) and expected risk of progression to end stage kidney failure and need of renal replacement therapy by dialysis or transplantation during the study period.
- Active systemic autoimmune diseases;
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 |
|---|---|---|
| Dapagliflozin 10Mg TabDapagliflozin 10 mg/die will be administered orally for six-weeks. | Drug | IMP |
| PlaceboPlacebo one tablet/die will be administered orally for six-weeks. | Other | Placebo |
Primary outcome
Glomerular Filtration rate (GFR)
Time frame: Changes from baseline and day 1, 8, 42,84, 92,126 and 140.
GFR measured by the Iohexol plasma clearance technique
24-hour urinary protein excretion
Time frame: Changes from start (day 0, day 84) and end (day 42, day 126) of each Treatment Period with dapagliflozin or placebo
24-hour urinary protein excretion will be measured as median of three measurements in three consecutive 24-hour urine collections
1 secondary outcome
Renal plasma flow (RPF)
Time frame: Changes from baseline and day 1, 8, 42,84, 92,126 and 140.
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 10 May 2024.
- Individual participant dataSharing planned: No
Related trials for Chronic Kidney Diseases
Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruiting
An Individuation Intervention to Reduce Socioeconomic Disparities in Chronic Kidney Disease Care
Chronic Kidney Diseases
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.
Giuseppe Remuzzi, MD study director
Istituto Di Ricerche Farmacologiche Mario Negri
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dapagliflozin 10Mg Tab in people with Chronic Kidney Diseases, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
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 12 inclusion and 16 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 10 May 2024. 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 Italy. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Glomerular Filtration rate (GFR) (time frame: Changes from baseline and day 1, 8, 42,84, 92,126 and 140.). 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 10 May 2024.