Last updated 21 months ago
Zibotentan and Dapagliflozin for the Treatment of CKD (ZENITH-CKD Trial)
542 patients around the world
Available in Argentina, United States, Brazil, Spain
The study will be conducted in approximately 220 sites in North America, South America,
Africa, Asia/Pacific, and European countries.
Participants will be randomized to 12 weeks of treatment plus 2 weeks follow-up.
After screening, eligible participants will be stratified by diabetes (diabetic kidney
disease [DKD] versus non-diabetes mellitus [non-DM] CKD) and baseline eGFR (below or
equal versus above 45 mL/min/1.73m^2).
A total of 495 participants will be randomised into this study, including participants
randomised under the earlier study design. Four hundred and fifteen (415) participants
will be randomised to have 166 participants in zibotentan Dose A/dapagliflozin 10 mg
combination arm and dapagliflozin 10 mg monotherapy arm, and 83 participants in the
zibotentan Dose B/dapagliflozin 10 mg combination arm.
- Zibotentan Dose A + Dapagliflozin 10 mg once daily.
- Zibotentan Dose B + Dapagliflozin 10 mg once daily.
- Placebo + Dapagliflozin 10 mg once daily
Participants who were previously randomised cannot be re-randomised.
AstraZeneca
1Research sites
542Patients around the world
Requirements for the patient
To 130 Years
All Gender
Medical requirements
- Diagnosis of CKD, defined as: (a) eGFR chronic kidney disease epidemiology collaboration (CKD-EPI) ≥ 20 mL/min/1.73 m^2, and (b) UACR ≥ 150 and ≤ 5000 mg albumin/g creatinine, based on a single first morning void spot urine sample at screening.No current or prior (within 1 month of screening) medical treatment with an SGLT2i (sodium-glucose co-transporter 2 inhibitor) or any fixed dose combination with SGLT2iIf ACEi and/or ARB and/or mineralocorticoid receptor agonist (MRA) are prescribed, the dose must be stable ≥ 4 weeks before screening. Participants who have been deemed unable to tolerate ACEi or ARB therapy due to allergy or complications can be enrolledNo current or prior treatment within 6 months prior to screening with cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary kidney diseaseBody mass index (BMI) ≤ 40 kg/m^2All participants should follow protocol defined contraceptives procedures
- Minimal change disease, unstable rapidly progressing renal disease, and/or renal disease requiring significant immunosuppression, autosomal dominant or autosomal recessive polycystic kidney diseaseParticipants with New York Heart Association classification functional heart failure (HF) class III or IVAcute coronary syndrome events within 3 months prior to screeningParticipants with a B-type natriuretic peptide (BNP) ≥ 200 pg/mL or NT-proBNP ≥ 600 pg/mL (BNP ≥ 400 pg/mL or NT-proBNP ≥ 1200 pg/mL, respectively, if associated with atrial fibrillation) measured by local laboratory at screening (Visit 1)Participants with unstable HF requiring hospitalisation for optimisation of HF treatment and/or who have not been stable on HF therapy within 6 months prior to screeningHeart failure due to cardiomyopathies that would primarily require other specific treatment: eg, cardiomyopathy due to pericardial disease, amyloidosis or other infiltrative diseases, cardiomyopathy related to congenital heart disease, primary hypertrophic cardiomyopathy, cardiomyopathy related to toxic or infective conditionsHigh output HFHeart failure due to primary cardiac valvular disease/dysfunction, severe functional mitral or tricuspid valve insufficiency, or planned cardiac valve repair/replacementParticipants with uncontrolled diabetes mellitus (HbA1c > 12%), and with T1DMIntermittent or persistent second or third degree atrioventricular block after sinus node dysfunction, with clinically significant bradycardia or sinus pause when not treated with pacemakerHistory of any life-threatening cardiac dysrhythmiaCardiac surgery or non-elective percutaneous coronary interventions (within 3 months) or open chest coronary artery bypass grafting or valvular repair/replacement (within 12 months) prior to screening or is planned to undergo any of these procedures after randomisationHeart transplantation or left ventricular assist device at any timeHistory or ongoing allergy/hypersensitivity, as judged by the investigator, to SGLT2i or drugs with a similar chemical structure to zibotentanAny clinically significant disease or disorder, which might put the participant at risk because of participation in the study, or probable alternative primary reason for participant's symptoms in judgment of investigator, including but not limited to: Isolated pulmonary arterial hypertension (defined as mean PAP ≥ 25 mmHg at rest) or right ventricular failure; in the absence of left-sided HF, Anaemia defined as haemoglobin (Hb) level < 100 g/L or 10 g/dL at screening (Visit 1), Severe chronic obstructive pulmonary disease or other lung disease including but not limited to pulmonary fibrosis requiring chronic oxygen therapy, regular nebuliser use, or oral steroid therapyStroke, transient ischemic attack, carotid surgery, or carotid angioplasty within previous 3 months prior to screening Severe hepatic impairment (Child-Pugh class C Hepatic impairment), aspartate transaminase or alanine transaminase > 2x the upper limit of normal [ULN]; or total bilirubin > 2x ULN at time of screeningParticipants with newly detected pathological laboratory values or an ongoing disease condition requiring investigation and/or initiation or adjustment of current treatmentPositive hepatitis C antibody, or hepatitis B virus, surface antigen at screeningParticipants treated with strong or moderate CYP3A4 inhibitor or inducerConfirmation of corona virus disease- 2019 (COVID-19) infection: Participant has a positive test result for severe acute respiratory syndrome coronavirus 2 during screening. Participants who are not hospitalised for COVID-19 infections can be re screened 4 weeks after they have recovered, Participant has been previously hospitalised with COVID-19 infectionEjection fraction < 50% measured by echocardiogram at screening
Sites
CENTRO DE ESTUDIOS CLÍNICOS SKY SPA
Recruiting
StudyZENITH-CKD
SponsorAstraZeneca
Study typeInterventional
Requirements
To 130 YearsAll Gender
Unique study IDclinicaltrials.gov
NCT04724837
