Heart FailurePhase 2MIRACLENCT04595370
Efficacy, Safety and Tolerability of AZD9977 and Dapagliflozin in Participants With Heart Failure and Chronic Kidney Disease
A Phase 2 study testing AZD9977 and Dapagliflozin in people with Heart Failure and Chronic Kidney Disease, run by AstraZeneca at 156 sites in 22 countries.
Trial summary
The purpose of the study is to evaluate the efficacy and safety of AZD9977 in combination with dapagliflozin compared with dapagliflozin alone and to assess the dose-response relationship, dapagliflozin alone and 3 doses of AZD9977 combined with dapagliflozin on urinary albumin to creatinine ratio (UACR). Read more about this study
- Who is it for?
- Ages 21 to 130 years
- Conditions the study is for
- Heart Failure, Chronic Kidney Disease
- What is being tested?
- AZD9977 and Dapagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 153 participants
- Where
- 156 sitesin 22 countries
- Study dates
- 26 Jan 2021to 22 Sep 2023
- Phase
- Phase 2
- 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 21 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants are included in the study if any of the following criteria apply:
- Documented diagnosis of stable symptomatic HF (New York Heart Association class II-III) at screening, and a medical history of typical symptoms and signs of HF in those who are currently receiving loop diuretic treatment
- Left ventricular ejection fraction <60% documented by the most recent echocardiogram or cardiac magnetic resonance imaging within the last 12 months prior to screening
- Stable background treatment for HF, hypertension, diabetes mellitus or renal disease according to guidelines
- N-terminal-pro-brain natriuretic peptide (NT proBNP) ≥300 pg/mL for participants with sinus rhythm at screening; and NT proBNP ≥600 pg/mL for participants with atrial fibrillation/flutter at screening
- The eGFR ≥30 and ≤60 mL/min/1.73^2 (by CKD- EPI formula) and UACR ≥30 mg/g (3 mg/mmol) and <3000 mg/g (300 mg/mmol)
Show all 12Show fewer
- Body mass index less than 40 kg/m^2
- Serum/plasma K+ level ≥ 3.5 and < 5.0 mmol/L within 10 days prior to randomization
- Serum/ plasma Na+ level within normal reference values within 10 days prior to randomization
- Systolic blood pressure should be at protocol defined range at randomization (Visit 3), with no change to antihypertensive treatments in previous 3 weeks
- Male or female of non-childbearing potential
- All participants must follow protocol defined contraceptives procedures
Who cannot join
- Participants are excluded from the study if any of the following criteria apply:
- Primary glomerulopathy, vasculitic renal disease, prior dialysis or unstable rapidly progressing renal disease, autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or anti-neutrophil cytoplasm antibody-associated vasculitis
- Participants with currently decompensated HF requiring hospitalization for optimization of HF treatment and are not on stable HF therapy at the time of enrollment
- HF due to cardiomyopathies
- High output HF (e.g., due to hyperthyroidism or Paget's disease)
- HF due to pericardial disease, congenital heart disease or clinically significant uncorrected primary cardiac valvular disease or planned cardiac valve repair/replacement
Show all 23Show fewer
- Participants with uncontrolled diabetes mellitus (Glycated hemoglobin >10%)
- Participants with Type 1 diabetes mellitus
- Intermittent or persistent 2nd or 3rd degree atrioventricular block, sinus node dysfunction with clinically significant bradycardia or sinus pauses, not treated with a pacemaker
- History of any life-threatening cardiac dysrhythmia or uncontrolled ventricular rate in participants with atrial fibrillation or atrial flutter
- Acute coronary syndrome and/or elective/non-elective percutaneous cardiac interventions (within 3 months) prior to randomisation or is planned to undergo any of these procedures during the study
- Any major cardiovascular (eg, open chest, coronary artery bypass grafting or valvular repair/replacement) or major non-cardiovascular surgery within 3 months prior to randomisation or is planned to undergo any cardiovascular surgery during the study
- Heart transplantation or left ventricular assist device at any time or if these are planned
- Kidney or any organ transplantation or if these are planned
- Medical conditions associated with development of hyperkalaemia (Addison's disease )
- History or ongoing allergy/hypersensitivity, to sodium-glucose co-transporter-2 inhibitor (SGLT2i e.g., dapagliflozin, empagliflozin)
- Stroke, transient ischemic attack, carotid surgery, or carotid angioplasty within previous 3 months prior to randomisation
- Hepatic disease, including hepatitis and/or hepatic impairment (Child-Pugh class A-C), and aspartate aminotransferase or alanine transaminase or total bilirubin should be in protocol defined range at time of screening and/ or within 7 days prior to randomization
- Participants with newly detected pathological laboratory values or an ongoing disease condition
- If the participants clinical signs and symptoms consistent with COVID-19, and has been previously hospitalized with COVID-19 infection and did not fully recover their previous health status
- Previous randomization in the present study
- Prior medical treatment with an mineralocorticoid receptor antagonist where the medication was taken within 90 days prior to screening
- Current or prior treatment within 6 months prior to screening with cytotoxic therapy, immunosuppressive therapy, or other immunotherapy
Trial locations and contacts
156 sites in 22 countries.
156 sites in 22 countries
United States26 sites
Research Site
Augusta, Georgia, 30904
Research Site
Baltimore, Maryland, 21287
Research Site
Beverly Hills, California, 90211
Research Site
Columbus, Georgia, 31904
Research Site
Fountain Valley, California, 92708
Research Site
Hialeah, Florida, 33016
Research Site
Homestead, Florida, 33032
Research Site
Houston, Texas, 77087
Research Site
Houston, Texas, 77099
Research Site
Jacksonville, Florida, 32216
Research Site
Kingwood, Texas, 77339
Research Site
McKinney, Texas, 75069
Research Site
Memphis, Tennessee, 38119
Research Site
Methuen, Massachusetts, 01844
Research Site
Miami, Florida, 33155
Research Site
New Bern, North Carolina, 28562
Research Site
Northridge, California, 91324
Research Site
Ocala, Florida, 34474
Research Site
Rapid City, South Dakota, 57701
Research Site
San Antonio, Texas, 78207
Research Site
Sherman, Texas, 75092
Research Site
South Gate, California, 90280
Research Site
St Louis, Missouri, 63136
Research Site
Tampa, Florida, 33603
Research Site
The Bronx, New York, 10455
Research Site
Webster, Texas, 77598
Japan22 sites
Research Site
Chūōku, 103-0027
Research Site
Hamada-shi, 697-8511
Research Site
Hamamatsu, 430-0929
Research Site
Hanyu-shi, 348-8505
Research Site
Kasugai-shi, 487-0016
Research Site
Kawaguchi, 333-0842
Research Site
Kishiwada-shi, 596-8522
Research Site
Kobe, 650-0047
Research Site
Kobe, 654-0155
Research Site
Matsudo-Shi, 271-0077
Research Site
Matsumoto-shi, 390-8621
Research Site
Ono, 675-1392
Research Site
Osaka, 530-0001
Research Site
Sapporo, 006-0811
Research Site
Sayama, 350-1305
Research Site
tabashi City, 173-8610
Research Site
Takasago-shi, 676-0812
Research Site
Takasaki-shi, 370-0829
Research Site
Ueda-shi, 386-8610
Research Site
Yokohama, 231-8682
Research Site
Yokohama, 234-8503
Research Site
Yokohama, 236-0004
Poland17 sites
Research Site
Gdansk, 80-382
Research Site
Gdansk, 80-952
Research Site
Katowice, 40-040
Research Site
Lodz, 90-127
Research Site
Lodz, 92-213
Research Site
Lodz, 95-513
Research Site
Lublin, 20-709
Research Site
Oława, 55-200
Research Site
Ostrowiec Świętokrzyski, 27-400
Research Site
Oświęcim, 32-600
Research Site
Pabianice, 95-200
Research Site
Poznan, 60-702
Research Site
Skorzewo, 60-185
Research Site
Sopot, 81-717
Research Site
Szczecin, 71-434
Research Site
Torun, 87-100
Research Site
Warsaw, 01-192
Russia11 sites
Research Site
Kazan, Tatarstan, 420012
Research Site
Kazan', 420101
Research Site
Kemerovo, 650002
Research Site
Moscow, 111539
Research Site
Moscow, 121552
Research Site
Moscow, 125284
Research Site
Moscow, 129110
Research Site
Saint Petersburg, 195067
Research Site
Saint Petersburg, 195257
Research Site
Saint Petersburg, 197022
Research Site
Saint Petersburg, 197089
Bulgaria10 sites
Research Site
Pleven, 5800
Research Site
Plovdiv, 1606
Research Site
Plovdiv, 4002
Research Site
Plovdiv, 4003
Research Site
Sofia, 1233
Research Site
Sofia, 1309
Research Site
Sofia, 1431
Research Site
Sofia, 1510
Research Site
Sofia, 1784
Research Site
Veliko Tarnovo, 5000
Spain9 sites
Research Site
A Coruña, 15006
Research Site
Barcelona, 08003
Research Site
El Palmar, 30120
Research Site
Madrid, 28041
Research Site
Málaga, 29010
Research Site
Santiago(A Coruña), 15706
Research Site
Seville, 41009
Research Site
Valencia, 46010
Research Site
Valencia, 46026
Hungary6 sites
Research Site
Balatonfüred, 8230
Research Site
Budapest, 1036
Research Site
Budapest, 1122
Research Site
Debrecen, 4032
Research Site
Miskolc, 3530
Research Site
Orosháza, H-5900
Slovakia6 sites
Research Site
Banská Bystrica, 974 01
Research Site
Brezno, 977 01
Research Site
Lučenec, 984 01
Research Site
Prešov, 080 01
Research Site
Svidník, 08901
Research Site
Trenčín, 911 01
South Korea6 sites
Research Site
Busan, 49201
Research Site
Gangwon-do, 26426
Research Site
Seongnam-si, 463-707
Research Site
Seoul, 03080
Research Site
Seoul, 06351
Research Site
Seoul, 06591
Taiwan5 sites
Research Site
Kaohsiung City, 80756
Research Site
Taichung, 40201
Research Site
Taipei, 10449
Research Site
Taipei, 110
Research Site
Taipei, 11217
Canada4 sites
Research Site
Montreal, Quebec, H2X 0A9
Research Site
Peterborough, Ontario, K9J 0B2
Research Site
Québec, Quebec, G1R 2J6
Research Site
Toronto, Ontario, M4N 3M5
Czechia4 sites
Research Site
Pardubice, 532 03
Research Site
Prague, 120 00
Research Site
Prague, 158 00
Research Site
Uherské Hradiště, 68601
Germany4 sites
Research Site
Dresden, 1307
Research Site
Frankfurt, 60313
Research Site
Jena, 07747
Research Site
Leipzig, 04103
India4 sites
Research Site
Ahmedabad, 382421
Research Site
Chennai, 600081
Research Site
Kolkata, 700020
Research Site
Pune, 411011
Lithuania4 sites
Research Site
Kaunas, 50177
Research Site
Klaipėda, 92231
Research Site
Šiauliai, LT-76231
Research Site
Vilnius, 08661
Sweden4 sites
Research Site
Gothenburg, 413 46
Research Site
Stockholm, 14186
Research Site
Stockholm, 18288
Research Site
Uppsala, 75185
Thailand4 sites
Research Site
Bangkok, 10400
Research Site
Bangkok, 10700
Research Site
Chaingmai, 50200
Research Site
Khon Kaen, 40002
Denmark3 sites
Research Site
Aarhus, 8200
Research Site
Herlev, 2730
Research Site
Svendborg, 5700
Ukraine3 sites
Research Site
Ivano-Frankivsk, 76018
Research Site
Kharkiv, 61039
Research Site
Kyiv, 02091
Turkey (Türkiye)2 sites
Research Site
Adana, 01060
Research Site
Kocaeli, 41380
About this study
Official title: A Phase 2b, Randomised, Double-Blind, Active Controlled, Multi Centre Study to Evaluate the Efficacy, Safety and Tolerability of Oral AZD9977 and Dapagliflozin Treatment in Patients With Heart Failure and Chronic Kidney Disease
The purpose of the study is to evaluate the efficacy and safety of AZD9977 in combination with dapagliflozin compared with dapagliflozin alone and to assess the dose-response relationship, dapagliflozin alone and 3 doses of AZD9977 combined with dapagliflozin on urinary albumin to creatinine ratio (UACR). The study will be conducted in participants with heart failure (HF) with left ventricular ejection fraction (LVEF [below 60%]) and chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR [between ≥ 20 and ≤ 60 mL/min/1.73 m^2, with at least 20% of participants with eGFR ≥ 20 to <30 mL/min/1.73^2 and a maximum of 35% of participants with eGFR ≥ 45 mL/min/1.73 m^2]).
Read the detailed description
After screening, eligible participants will undergo a run-in period where all participants receive dapagliflozin for up to 7 weeks depending on pre-study use of SGLT2i or not. At the end of the run-in period, eligible participants will be randomly assigned with a 1:1:1:1 ratio to receive once daily administration of one of the following 4 study treatments group for 12 weeks. To ensure blinding, the study treatment will be administered in the form of 3 oral capsules of AZD9977 or placebo and 1 oral tablet or dapagliflozin.
- AZD9977 Dose A + dapagliflozin 10 mg
- AZD9977 Dose B + dapagliflozin 10 mg
- AZD9977 Dose C + dapagliflozin 10 mg
- Dapagliflozin 10 mg
Participants will be randomized to one of the above treatment group, according to type 2 diabetes mellitus [T2DM (yes/no)] and eGFR (≥ 20 to <30 mL/min/1.73^2; or ≥ 30 to < 45 mL/min/1.73^2; or ≥45 mL/min/1.73^2).
The total duration of participation will be approximately 22 to 24weeks.
- Conditions
- Heart Failure, Chronic Kidney Disease
- Being tested
- AZD9977, Dapagliflozin
- Keywords
- Heart Failure, Type 2 diabetes mellitus, Diabetic kidney disease, Chronic kidney disease, Mineralocorticoid receptor modulator, Sodium-glucose co-transporter-2 inhibitor, AZD9977, Dapagliflozin, Urinary albumin creatinine ratio
- Medical subject headings
- Heart Failure, Renal Insufficiency, Chronic, Diabetes Mellitus, Type 2, Diabetic Nephropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9977Drug
Participants will receive AZD9977 as per the arms they are randomized.
DapagliflozinDrug
Participants will receive dapagliflozin as per the arms they are randomized.
| Study group | Role | What they receive |
|---|---|---|
| AZD9977 Dose A + dapagliflozin 10 mg | Experimental | Participants will receive once daily oral dose A of AZD9977 and 10 mg dapagliflozin for 12 weeks. Receives: Drug: AZD9977; Drug: Dapagliflozin |
| AZD9977 Dose B + dapagliflozin 10 mg | Experimental | Participants will receive once daily oral dose B of AZD9977 and 10 mg dapagliflozin for 12 weeks. Receives: Drug: AZD9977; Drug: Dapagliflozin |
| AZD9977 Dose C + dapagliflozin 10 mg | Experimental | Participants will receive once daily oral dose C of AZD9977 and 10 mg dapagliflozin for 12 weeks. Receives: Drug: AZD9977; Drug: Dapagliflozin |
| Dapagliflozin 10 mg | Experimental | Participants will receive once daily oral dose of dapagliflozin 10 mg alone for 12 weeks. Receives: Drug: Dapagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12
The effect of AZD9977 in combination with dapagliflozin compared with dapagliflozin alone on UACR assessed. Urine samples were collected for the analysis of UACR. UACR (milligrams per gram [mg/g]) was calculated as 10 x urine albumin (mg per deciliter [mg/dL])/urine creatinine (g/dL). Change from baseline in UACR at the end of 12 weeks of study treatment was calculated as the average of the UACR values at Week 12 and was analyzed by a mixed-effects model for repeated measures (MMRM). Due to early removal of arms (AZD9977 150 mg monotherapy and Placebo), the study objectives were revised and the MMRM analysis included the 4 remaining arms (AZD9977 15 mg + Dapagliflozin, AZD9977 50 mg + Dapagliflozin, AZD9977 150 mg + Dapagliflozin, and Dapagliflozin 10 mg). Since 2 arms were removed from the study resulting in fewer participants only descriptive statistics are shown for those two arms without formal comparison.
Measured: Baseline (Day 1) to Week 12
Secondary outcomes (6)
Percent Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at 12 Weeks to Assess Dose-Response Relationship
The dose-response relationship of dapagliflozin alone and 3 doses of AZD9977 combined with dapagliflozin on UACR was assessed. Urine samples were collected for the analysis of UACR. UACR (mg/g) was calculated as 10 x urine albumin (mg/dL)/urine creatinine (g/dL). Change from baseline in UACR at the end of 12 weeks of study treatment was calculated as the average of the UACR values at Week 12 and was analyzed by a mixed-effects model for repeated measures (MMRM). Due to early removal of arms (AZD9977 150 mg monotherapy and Placebo), the study objectives were revised and the MMRM analysis included the 4 remaining arms (AZD9977 15 mg + Dapagliflozin, AZD9977 50 mg + Dapagliflozin, AZD9977 150 mg + Dapagliflozin, and Dapagliflozin 10 mg). Since 2 arms were removed from the study resulting in fewer participants, only descriptive statistics was shown for those two arms without formal comparison.
Measured: Baseline (Day 1) to Week 12
Number of Participants With Adverse Events (AEs)
The safety and tolerability of AZD9977 combined with dapagliflozin 10 mg, AZD9977 monotherapy, dapagliflozin 10 mg monotherapy and placebo was assessed.
Measured: From baseline (Day 1) until Day 113
Change From Baseline in Serum Potassium (K+)
Effect of AZD9977 combined with dapagliflozin 10 mg, AZD9977 monotherapy, dapagliflozin 10 mg monotherapy and placebo on serum K+ was assessed.
Measured: Baseline (Day 1) and Week 12
Absolute Value of Serum Potassium Over Time
Effect of AZD9977 combined with dapagliflozin 10 mg, AZD9977 monotherapy, dapagliflozin 10 mg monotherapy and placebo on serum K+ was assessed.
Measured: Baseline (Day 1) and Week 12
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Effect of AZD9977 combined with dapagliflozin 10 mg, AZD9977 monotherapy, dapagliflozin 10 mg monotherapy and placebo on eGFR was assessed.
Measured: Baseline (Day 1) and Week 12
Absolute Value of eGFR Over Time
Effect of all doses of AZD9977 combined with dapagliflozin 10 mg, AZD9977 monotherapy, dapagliflozin 10 mg monotherapy and placebo on eGFR was assessed
Measured: Baseline (Day 1) to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2020
- Study start26 Jan 2021
- Primary completion22 Sep 2023
- Study completion22 Sep 2023
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 Heart FailureStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe 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
- Parallel groups
- Model description
- Participants who meet the eligibility criteria will be randomized to one of the following treatment group: 1. AZD9977 Dose A + dapagliflozin 10 mg 2. AZD9977 Dose B + dapagliflozin 10 mg 3. AZD9977 Dose C + dapagliflozin 10 mg 4. Dapagliflozin 10 mg
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 153 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John McMurray, Principal investigator, University of Glasgow, United Kingdom
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04595370
- Sponsor's protocol ID
- D6402C00001
- Other IDs
- 2020-003126-23
- Acronym
- MIRACLE
- Status last verified
- Oct 2024
- First submitted
- 14 Oct 2020
- Last updated
- 19 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2b, Randomised, Double-Blind, Active Controlled, Multi Centre Study to Evaluate the Efficacy, Safety and Tolerability of Oral AZD9977 and Dapagliflozin Treatment in Patients With Heart Failure and Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT04595370
- Acronym / sponsor ID
- MIRACLE / D6402C00001
- Conditions
- Heart Failure, Chronic Kidney Disease
- Keywords
- Heart Failure, Type 2 diabetes mellitus, Diabetic kidney disease, Chronic kidney disease, Mineralocorticoid receptor modulator, Sodium-glucose co-transporter-2 inhibitor, AZD9977, Dapagliflozin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 153 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 26 Jan 2021 (actual)
- Primary completion
- 22 Sep 2023 (actual)
- Study completion
- 22 Sep 2023 (actual)
- First posted
- 20 Oct 2020 (actual)
- Results
- Posted 19 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to evaluate the efficacy and safety of AZD9977 in combination with dapagliflozin compared with dapagliflozin alone and to assess the dose-response relationship, dapagliflozin alone and 3 doses of AZD9977 combined with dapagliflozin on urinary albumin to creatinine ratio (UACR). The study will be conducted in participants with heart failure (HF) with left ventricular ejection fraction (LVEF [below 60%]) and chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR [between ≥ 20 and ≤ 60 mL/min/1.73 m^2, with at least 20% of participants with eGFR ≥ 20 to <30 mL/min/1.73^2 and a maximum of 35% of participants with eGFR ≥ 45 mL/min/1.73 m^2]).
Detailed description
After screening, eligible participants will undergo a run-in period where all participants receive dapagliflozin for up to 7 weeks depending on pre-study use of SGLT2i or not. At the end of the run-in period, eligible participants will be randomly assigned with a 1:1:1:1 ratio to receive once daily administration of one of the following 4 study treatments group for 12 weeks. To ensure blinding, the study treatment will be administered in the form of 3 oral capsules of AZD9977 or placebo and 1 oral tablet or dapagliflozin.
- AZD9977 Dose A + dapagliflozin 10 mg
- AZD9977 Dose B + dapagliflozin 10 mg
- AZD9977 Dose C + dapagliflozin 10 mg
- Dapagliflozin 10 mg
Participants will be randomized to one of the above treatment group, according to type 2 diabetes mellitus [T2DM (yes/no)] and eGFR (≥ 20 to <30 mL/min/1.73^2; or ≥ 30 to < 45 mL/min/1.73^2; or ≥45 mL/min/1.73^2).
The total duration of participation will be approximately 22 to 24weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Participants who meet the eligibility criteria will be randomized to one of the following treatment group: 1. AZD9977 Dose A + dapagliflozin 10 mg 2. AZD9977 Dose B + dapagliflozin 10 mg 3. AZD9977 Dose C + dapagliflozin 10 mg 4. Dapagliflozin 10 mg
| Arm | Type | Receives |
|---|---|---|
| AZD9977 Dose A + dapagliflozin 10 mg | Experimental | Drug: AZD9977, Drug: DapagliflozinParticipants will receive once daily oral dose A of AZD9977 and 10 mg dapagliflozin for 12 weeks. |
| AZD9977 Dose B + dapagliflozin 10 mg | Experimental | Drug: AZD9977, Drug: DapagliflozinParticipants will receive once daily oral dose B of AZD9977 and 10 mg dapagliflozin for 12 weeks. |
| AZD9977 Dose C + dapagliflozin 10 mg | Experimental | Drug: AZD9977, Drug: DapagliflozinParticipants will receive once daily oral dose C of AZD9977 and 10 mg dapagliflozin for 12 weeks. |
| Dapagliflozin 10 mg | Experimental | Drug: DapagliflozinParticipants will receive once daily oral dose of dapagliflozin 10 mg alone for 12 weeks. |
Who may qualify
- Ages
- 21 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Documented diagnosis of stable symptomatic HF (New York Heart Association class II-III) at screening, and a medical history of typical symptoms and signs of HF in those who are currently receiving loop diuretic treatment
- Left ventricular ejection fraction <60% documented by the most recent echocardiogram or cardiac magnetic resonance imaging within the last 12 months prior to screening
- Stable background treatment for HF, hypertension, diabetes mellitus or renal disease according to guidelines
- N-terminal-pro-brain natriuretic peptide (NT proBNP) ≥300 pg/mL for participants with sinus rhythm at screening; and NT proBNP ≥600 pg/mL for participants with atrial fibrillation/flutter at screening
- The eGFR ≥30 and ≤60 mL/min/1.73^2 (by CKD- EPI formula) and UACR ≥30 mg/g (3 mg/mmol) and <3000 mg/g (300 mg/mmol)
Key exclusion criteria (23 listed)
- Primary glomerulopathy, vasculitic renal disease, prior dialysis or unstable rapidly progressing renal disease, autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or anti-neutrophil cytoplasm antibody-associated vasculitis
- Participants with currently decompensated HF requiring hospitalization for optimization of HF treatment and are not on stable HF therapy at the time of enrollment
- HF due to cardiomyopathies
- High output HF (e.g., due to hyperthyroidism or Paget's disease)
- HF due to pericardial disease, congenital heart disease or clinically significant uncorrected primary cardiac valvular disease or planned cardiac valve repair/replacement
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 |
|---|---|---|
| AZD9977Participants will receive AZD9977 as per the arms they are randomized. | Drug | AZD9977 Dose A + dapagliflozin 10 mg, AZD9977 Dose B + dapagliflozin 10 mg, AZD9977 Dose C + dapagliflozin 10 mg |
| DapagliflozinParticipants will receive dapagliflozin as per the arms they are randomized. | Drug | AZD9977 Dose A + dapagliflozin 10 mg, AZD9977 Dose B + dapagliflozin 10 mg, AZD9977 Dose C + dapagliflozin 10 mg, Dapagliflozin 10 mg |
Primary outcome
Percent Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12
Time frame: Baseline (Day 1) to Week 12
The effect of AZD9977 in combination with dapagliflozin compared with dapagliflozin alone on UACR assessed. Urine samples were collected for the analysis of UACR. UACR (milligrams per gram [mg/g]) was calculated as 10 x urine albumin (mg per deciliter [mg/dL])/urine creatinine (g/dL). Change from baseline in UACR at the end of 12 weeks of study treatment was calculated as the average of the UACR values at Week 12 and was analyzed by a mixed-effects model for repeated measures (MMRM). Due to early removal of arms (AZD9977 150 mg monotherapy and Placebo), the study objectives were revised and the MMRM analysis included the 4 remaining arms (AZD9977 15 mg + Dapagliflozin, AZD9977 50 mg + Dapagliflozin, AZD9977 150 mg + Dapagliflozin, and Dapagliflozin 10 mg). Since 2 arms were removed from the study resulting in fewer participants only descriptive statistics are shown for those two arms without formal comparison.
6 secondary outcomes
Percent Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at 12 Weeks to Assess Dose-Response Relationship
Time frame: Baseline (Day 1) to Week 12
Number of Participants With Adverse Events (AEs)
Time frame: From baseline (Day 1) until Day 113
Change From Baseline in Serum Potassium (K+)
Time frame: Baseline (Day 1) and Week 12
Absolute Value of Serum Potassium Over Time
Time frame: Baseline (Day 1) and Week 12
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Time frame: Baseline (Day 1) and Week 12
Absolute Value of eGFR Over Time
Time frame: Baseline (Day 1) to Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Redacted CSR Synopsis\_D6402C00001Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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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.
John McMurray principal investigator
University of Glasgow, United Kingdom
156 sites in 22 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD9977 and Dapagliflozin in people with Heart Failure and Chronic Kidney Disease, run by AstraZeneca at 156 sites in 22 countries.
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 23 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 19 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 156 sites in United States, Japan, Poland, Russia, Bulgaria and 17 more countries. 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 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?
Yes. Results are posted in the registry (first posted 19 Nov 2024). 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?
Percent Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12 (time frame: Baseline (Day 1) to Week 12). 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 19 Nov 2024.