Efficacy, Safety and Tolerability of AZD9977 and Dapagliflozin in Participants With Heart Failure and Chronic Kidney Disease
MIRACLE
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
2 other identifiers
interventional
153
22 countries
156
Brief 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). 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 \[between ≥ 20 and ≤ 60 mL/min/1.73 m\^2, with at least 20% of participants with eGFR ≥ 20 to \<30 mL/min/1.73\^2 and a maximum of 35% of participants with eGFR ≥ 45 mL/min/1.73 m\^2\]).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 heart-failure
Started Jan 2021
Typical duration for phase_2 heart-failure
156 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 14, 2020
CompletedFirst Posted
Study publicly available on registry
October 20, 2020
CompletedStudy Start
First participant enrolled
January 26, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 22, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
September 22, 2023
CompletedResults Posted
Study results publicly available
November 19, 2024
CompletedNovember 19, 2024
October 1, 2024
2.7 years
October 14, 2020
September 20, 2024
October 28, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
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
Baseline (Day 1) to Week 12
Number of Participants With Adverse Events (AEs)
From baseline (Day 1) until Day 113
Change From Baseline in Serum Potassium (K+)
Baseline (Day 1) and Week 12
Absolute Value of Serum Potassium Over Time
Baseline (Day 1) and Week 12
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Baseline (Day 1) and Week 12
- +1 more secondary outcomes
Study Arms (4)
AZD9977 Dose A + dapagliflozin 10 mg
EXPERIMENTALParticipants will receive once daily oral dose A of AZD9977 and 10 mg dapagliflozin for 12 weeks.
AZD9977 Dose B + dapagliflozin 10 mg
EXPERIMENTALParticipants will receive once daily oral dose B of AZD9977 and 10 mg dapagliflozin for 12 weeks.
AZD9977 Dose C + dapagliflozin 10 mg
EXPERIMENTALParticipants will receive once daily oral dose C of AZD9977 and 10 mg dapagliflozin for 12 weeks.
Dapagliflozin 10 mg
EXPERIMENTALParticipants will receive once daily oral dose of dapagliflozin 10 mg alone for 12 weeks.
Interventions
Participants will receive AZD9977 as per the arms they are randomized.
Participants will receive dapagliflozin as per the arms they are randomized.
Eligibility Criteria
You may qualify if:
- 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)
- 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
You may not qualify if:
- 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
- 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 )
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (156)
Research Site
Beverly Hills, California, 90211, United States
Research Site
Fountain Valley, California, 92708, United States
Research Site
Northridge, California, 91324, United States
Research Site
South Gate, California, 90280, United States
Research Site
Hialeah, Florida, 33016, United States
Research Site
Homestead, Florida, 33032, United States
Research Site
Jacksonville, Florida, 32216, United States
Research Site
Miami, Florida, 33155, United States
Research Site
Ocala, Florida, 34474, United States
Research Site
Tampa, Florida, 33603, United States
Research Site
Augusta, Georgia, 30904, United States
Research Site
Columbus, Georgia, 31904, United States
Research Site
Baltimore, Maryland, 21287, United States
Research Site
Methuen, Massachusetts, 01844, United States
Research Site
St Louis, Missouri, 63136, United States
Research Site
The Bronx, New York, 10455, United States
Research Site
New Bern, North Carolina, 28562, United States
Research Site
Rapid City, South Dakota, 57701, United States
Research Site
Memphis, Tennessee, 38119, United States
Research Site
Houston, Texas, 77087, United States
Research Site
Houston, Texas, 77099, United States
Research Site
Kingwood, Texas, 77339, United States
Research Site
McKinney, Texas, 75069, United States
Research Site
San Antonio, Texas, 78207, United States
Research Site
Sherman, Texas, 75092, United States
Research Site
Webster, Texas, 77598, United States
Research Site
Roeselare, 8800, Belgium
Research Site
Pleven, 5800, Bulgaria
Research Site
Plovdiv, 1606, Bulgaria
Research Site
Plovdiv, 4002, Bulgaria
Research Site
Plovdiv, 4003, Bulgaria
Research Site
Sofia, 1233, Bulgaria
Research Site
Sofia, 1309, Bulgaria
Research Site
Sofia, 1431, Bulgaria
Research Site
Sofia, 1510, Bulgaria
Research Site
Sofia, 1784, Bulgaria
Research Site
Veliko Tarnovo, 5000, Bulgaria
Research Site
Peterborough, Ontario, K9J 0B2, Canada
Research Site
Toronto, Ontario, M4N 3M5, Canada
Research Site
Montreal, Quebec, H2X 0A9, Canada
Research Site
Québec, Quebec, G1R 2J6, Canada
Research Site
Pardubice, 532 03, Czechia
Research Site
Prague, 120 00, Czechia
Research Site
Prague, 158 00, Czechia
Research Site
Uherské Hradiště, 68601, Czechia
Research Site
Aarhus, 8200, Denmark
Research Site
Herlev, 2730, Denmark
Research Site
Svendborg, 5700, Denmark
Research Site
Dresden, 1307, Germany
Research Site
Frankfurt, 60313, Germany
Research Site
Jena, 07747, Germany
Research Site
Leipzig, 04103, Germany
Research Site
Balatonfüred, 8230, Hungary
Research Site
Budapest, 1036, Hungary
Research Site
Budapest, 1122, Hungary
Research Site
Debrecen, 4032, Hungary
Research Site
Miskolc, 3530, Hungary
Research Site
Orosháza, H-5900, Hungary
Research Site
Ahmedabad, 382421, India
Research Site
Chennai, 600081, India
Research Site
Kolkata, 700020, India
Research Site
Pune, 411011, India
Research Site
Roma, 00168, Italy
Research Site
Chūōku, 103-0027, Japan
Research Site
Hamada-shi, 697-8511, Japan
Research Site
Hamamatsu, 430-0929, Japan
Research Site
Hanyu-shi, 348-8505, Japan
Research Site
Itabashi-ku, 173-8610, Japan
Research Site
Kasugai-shi, 487-0016, Japan
Research Site
Kawaguchi, 333-0842, Japan
Research Site
Kishiwada-shi, 596-8522, Japan
Research Site
Kobe, 650-0047, Japan
Research Site
Kobe, 654-0155, Japan
Research Site
Matsudo-Shi, 271-0077, Japan
Research Site
Matsumoto-shi, 390-8621, Japan
Research Site
Ono, 675-1392, Japan
Research Site
Osaka, 530-0001, Japan
Research Site
Sapporo, 006-0811, Japan
Research Site
Sayama, 350-1305, Japan
Research Site
Takasago-shi, 676-0812, Japan
Research Site
Takasaki-shi, 370-0829, Japan
Research Site
Ueda-shi, 386-8610, Japan
Research Site
Yokohama, 231-8682, Japan
Research Site
Yokohama, 234-8503, Japan
Research Site
Yokohama, 236-0004, Japan
Research Site
Kaunas, 50177, Lithuania
Research Site
Klaipėda, 92231, Lithuania
Research Site
Šiauliai, LT-76231, Lithuania
Research Site
Vilnius, 08661, Lithuania
Research Site
Gdansk, 80-382, Poland
Research Site
Gdansk, 80-952, Poland
Research Site
Katowice, 40-040, Poland
Research Site
Lodz, 90-127, Poland
Research Site
Lodz, 92-213, Poland
Research Site
Lodz, 95-513, Poland
Research Site
Lublin, 20-709, Poland
Research Site
Ostrowiec Świętokrzyski, 27-400, Poland
Research Site
Oświęcim, 32-600, Poland
Research Site
Oława, 55-200, Poland
Research Site
Pabianice, 95-200, Poland
Research Site
Poznan, 60-702, Poland
Research Site
Skorzewo, 60-185, Poland
Research Site
Sopot, 81-717, Poland
Research Site
Szczecin, 71-434, Poland
Research Site
Torun, 87-100, Poland
Research Site
Warsaw, 01-192, Poland
Research Site
Kazan', 420101, Russia
Research Site
Kazan, Tatarstan, 420012, Russia
Research Site
Kemerovo, 650002, Russia
Research Site
Moscow, 111539, Russia
Research Site
Moscow, 121552, Russia
Research Site
Moscow, 125284, Russia
Research Site
Moscow, 129110, Russia
Research Site
Saint Petersburg, 195067, Russia
Research Site
Saint Petersburg, 195257, Russia
Research Site
Saint Petersburg, 197022, Russia
Research Site
Saint Petersburg, 197089, Russia
Research Site
Banská Bystrica, 974 01, Slovakia
Research Site
Brezno, 977 01, Slovakia
Research Site
Lučenec, 984 01, Slovakia
Research Site
Prešov, 080 01, Slovakia
Research Site
Svidník, 08901, Slovakia
Research Site
Trenčín, 911 01, Slovakia
Research Site
Busan, 49201, South Korea
Research Site
Gangwon-do, 26426, South Korea
Research Site
Seongnam-si, 463-707, South Korea
Research Site
Seoul, 03080, South Korea
Research Site
Seoul, 06351, South Korea
Research Site
Seoul, 06591, South Korea
Research Site
A Coruña, 15006, Spain
Research Site
Barcelona, 08003, Spain
Research Site
El Palmar, 30120, Spain
Research Site
Madrid, 28041, Spain
Research Site
Málaga, 29010, Spain
Research Site
Santiago(A Coruña), 15706, Spain
Research Site
Seville, 41009, Spain
Research Site
Valencia, 46010, Spain
Research Site
Valencia, 46026, Spain
Research Site
Gothenburg, 413 46, Sweden
Research Site
Stockholm, 14186, Sweden
Research Site
Stockholm, 18288, Sweden
Research Site
Uppsala, 75185, Sweden
Research Site
Kaohsiung City, 80756, Taiwan
Research Site
Taichung, 40201, Taiwan
Research Site
Taipei, 10449, Taiwan
Research Site
Taipei, 110, Taiwan
Research Site
Taipei, 11217, Taiwan
Research Site
Bangkok, 10400, Thailand
Research Site
Bangkok, 10700, Thailand
Research Site
Chaingmai, 50200, Thailand
Research Site
Khon Kaen, 40002, Thailand
Research Site
Adana, 01060, Turkey (Türkiye)
Research Site
Kocaeli, 41380, Turkey (Türkiye)
Research Site
Ivano-Frankivsk, 76018, Ukraine
Research Site
Kharkiv, 61039, Ukraine
Research Site
Kyiv, 02091, Ukraine
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
Enrolment stopped early because of slow recruitment. Therefore, pre-specified sample size of 500 and planned statistical power were not achieved. Nine subjects were excluded from analysis due to site misconduct and GCP non-compliance.
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Study Officials
- PRINCIPAL INVESTIGATOR
John McMurray
University of Glasgow, United Kingdom
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 14, 2020
First Posted
October 20, 2020
Study Start
January 26, 2021
Primary Completion
September 22, 2023
Study Completion
September 22, 2023
Last Updated
November 19, 2024
Results First Posted
November 19, 2024
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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.