Heart FailurePhase 1NCT03682497
Study in HFpEF Patients to Compare the Effect of AZD9977 and Spironolactone on Serum Potassium
A Phase 1 study testing AZD9977 and Spironolactone in people with Heart Failure, run by AstraZeneca at 18 sites in 4 countries.
Trial summary
This is a Phase I, Multicentre study to Compare the Effect of AZD9977 and Spironolactone on Serum Potassium [sK+] during 28 days in Patients with HFmrEF or HFpEF and eGFR in the range of ≥40 and ≤70 mL/min/1.73m2. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- AZD9977 and Spironolactone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 18 sitesin 4 countries
- Study dates
- 1 Nov 2018to 31 Mar 2020
- Phase
- Phase 1
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Symptoms and signs consistent with a diagnosis of heart failure (HF)
- Left ventricular ejection fraction (LVEF) ≥40% by transthoracic echocardiography within the past 12 months
- Plasma NT-proBNP level ≥125 pg/ml (≥ 600pg/mL if patient has persistent or permanent atrial fibrillation, atrial flutter, or atrial tachycardia)
- Estimated glomerular filtration rate (eGFR) ≥40 and ≤70ml/min/1.73m2 (by CKD-EPI formula).
- Baseline serum potassium (sK+) level ≥3.5 and ≤4.8mmol/l.
- Stable doses of the following medications at baseline for at least 4 weeks prior to randomisation:
- Angiotensin receptor blocker (ARB) or Angiotensin converting enzyme inhibitor (ACEi) Loop diuretic (up to a 120mg furosemide dose or equivalent
Who cannot join
- Patients with documented LVEF <40% at any time (i.e. patients with previously impaired LVEF that has now improved are not permitted).
- Patients experiencing acute decompensation of heart failure requiring hospital admission or escalation in therapy.
- Primary cardiomyopathy (e.g. constrictive, restrictive, infiltrative, toxic, hypertrophic, congenital or any primary cardiomyopathy in judgment of Investigator).
- Hyponatraemia, defined as serum Na+ <135 mmol/L at the time of enrollment.
- Persistent resting sinus tachycardia >110 bpm or sinus bradycardia <45bpm.
- Systolic blood pressure (BP) <110mmHg or >180mmHg.
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- Diastolic BP <60 mmHg or >100 mmHg.
- Patients previously intolerant to MRA (e.g. spironolactone or eplerenone) for any reason.
- Medical conditions associated with development of hyperkalaemia (e.g. Addison's disease).
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.0 times the upper limit of normal (ULN).
- Patients who have been taking an MR antagonist within 1 month prior to randomization.
Trial locations and contacts
18 sites in 4 countries.
18 sites in 4 countries
Czechia7 sites
Research Site
Brandýs nad Labem, 250 01
Research Site
Česká Lípa, 470 77
Research Site
Jaroměř, 551 01
Research Site
Louny, 440 01
Research Site
Pardubice, 530 02
Research Site
Prague, 130 00
Research Site
Prague, 140 59
Poland5 sites
Research Site
Katowice, 40-081
Research Site
Krakow, 31-202
Research Site
Legnica, 59-220
Research Site
Warsaw, 02-097
Research Site
Wroclaw, 50-981
Bulgaria3 sites
Research Site
Plovdiv, 4002
Research Site
Sofia, 1309
Research Site
Sofia, 1784
United Kingdom3 sites
Research Site
Hull, HU3 2JZ
Research Site
Leicester, LE3 9PQ
Research Site
Sheffield, S5 7AU
About this study
Official title: A Phase I, Open Label, Randomized, Parallel Group, Multicentre Study to Compare the Effect of AZD9977 and Spironolactone on Serum Potassium [sK+] During 28 Days in Patients With HFmrEF or HFpEF and eGFR in the Range of ≥40 and ≤70 mL/Min/1.73m2.
This is a Phase I, Multicentre study to Compare the Effect of AZD9977 and Spironolactone on Serum Potassium [sK+] during 28 days in Patients with HFmrEF or HFpEF and eGFR in the range of ≥40 and ≤70 mL/min/1.73m2.
- Conditions
- Heart Failure
- Being tested
- AZD9977, Spironolactone
- Keywords
- Heart failure., Oral selective mineralocorticoid receptor modulator., Heart failure with preserved ejection fraction (HFpEF).
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9977Drug
AZD9977 capsules taken orally for 28 days.
SpironolactoneDrug
Spironolactone tablets taken orally for 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Spironolactone | Active comparator | Spironolactone treatment for 28 days Receives: Drug: Spironolactone |
| AZD9977 | Experimental | AZD9977 treatment for 28 days Receives: Drug: AZD9977 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative change (%) from baseline in serum potassium
To compare the effect of AZD9977 with spironolactone on serum potassium (sK+)
Measured: Measurements on day 1, 7, 14, 21 and 28 will be used. The primary comparison between Spironolactone and AZD9977 will be done at day 28.
Secondary outcomes (2)
Plasma trough concentrations (Ctrough) values of spironolactone and AZD9977
To evaluate the pharmacokinetics (PK) of AZD9977 and spironolactone
Measured: PK samples will be taken (within 60 min prior to dose) at day 1, 7, 14, 21 and 28.
Relative change (%) from baseline in serum potassium
To compare the effects of AZD9977 with spironolactone on serum potassium at Day 14.
Measured: Measurements on day 1, 7 and 14 will be used. The primary comparison between Spironolactone and AZD9977 will be done at day 14.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2018
- Study start1 Nov 2018
- Primary completion31 Mar 2020
- Study completion31 Mar 2020
Why it stopped: Attendance at study sites carries risk of COVID-19 infection. Non-attendance at planned study site visits has unacceptable study related patient safety risk.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03682497
- Sponsor's protocol ID
- D6401C00004
- Status last verified
- Apr 2020
- First submitted
- 21 Sep 2018
- Last updated
- 1 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- 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 request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open Label, Randomized, Parallel Group, Multicentre Study to Compare the Effect of AZD9977 and Spironolactone on Serum Potassium [sK+] During 28 Days in Patients With HFmrEF or HFpEF and eGFR in the Range of ≥40 and ≤70 mL/Min/1.73m2.
- ClinicalTrials.gov ID
- NCT03682497
- Acronym / sponsor ID
- D6401C00004
- Conditions
- Heart Failure
- Keywords
- Heart failure., Oral selective mineralocorticoid receptor modulator., Heart failure with preserved ejection fraction (HFpEF).
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Attendance at study sites carries risk of COVID-19 infection. Non-attendance at planned study site visits has unacceptable study related patient safety risk.
- Enrolment
- 68 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 1 Nov 2018 (actual)
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 31 Mar 2020 (actual)
- First posted
- 24 Sep 2018 (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 I, Multicentre study to Compare the Effect of AZD9977 and Spironolactone on Serum Potassium [sK+] during 28 days in Patients with HFmrEF or HFpEF and eGFR in the range of ≥40 and ≤70 mL/min/1.73m2.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Spironolactone | Active comparator | Drug: SpironolactoneSpironolactone treatment for 28 days |
| AZD9977 | Experimental | Drug: AZD9977AZD9977 treatment for 28 days |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Symptoms and signs consistent with a diagnosis of heart failure (HF)
- Left ventricular ejection fraction (LVEF) ≥40% by transthoracic echocardiography within the past 12 months
- Plasma NT-proBNP level ≥125 pg/ml (≥ 600pg/mL if patient has persistent or permanent atrial fibrillation, atrial flutter, or atrial tachycardia)
- Estimated glomerular filtration rate (eGFR) ≥40 and ≤70ml/min/1.73m2 (by CKD-EPI formula).
- Baseline serum potassium (sK+) level ≥3.5 and ≤4.8mmol/l.
Key exclusion criteria (11 listed)
- Patients with documented LVEF <40% at any time (i.e. patients with previously impaired LVEF that has now improved are not permitted).
- Patients experiencing acute decompensation of heart failure requiring hospital admission or escalation in therapy.
- Primary cardiomyopathy (e.g. constrictive, restrictive, infiltrative, toxic, hypertrophic, congenital or any primary cardiomyopathy in judgment of Investigator).
- Hyponatraemia, defined as serum Na+ <135 mmol/L at the time of enrollment.
- Persistent resting sinus tachycardia >110 bpm or sinus bradycardia <45bpm.
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 |
|---|---|---|
| AZD9977AZD9977 capsules taken orally for 28 days. | Drug | AZD9977 |
| SpironolactoneSpironolactone tablets taken orally for 28 days. | Drug | Spironolactone |
Primary outcome
Relative change (%) from baseline in serum potassium
Time frame: Measurements on day 1, 7, 14, 21 and 28 will be used. The primary comparison between Spironolactone and AZD9977 will be done at day 28.
To compare the effect of AZD9977 with spironolactone on serum potassium (sK+)
2 secondary outcomes
Plasma trough concentrations (Ctrough) values of spironolactone and AZD9977
Time frame: PK samples will be taken (within 60 min prior to dose) at day 1, 7, 14, 21 and 28.
Relative change (%) from baseline in serum potassium
Time frame: Measurements on day 1, 7 and 14 will be used. The primary comparison between Spironolactone and AZD9977 will be done at day 14.
Results and safety
The study was stopped early (reason given: Attendance at study sites carries risk of COVID-19 infection. Non-attendance at planned study site visits has unacceptable study related patient safety risk.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2020.
- 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 request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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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.
The record lists no contact. Use the official record to reach the sponsor.
18 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD9977 and Spironolactone in people with Heart Failure, run by AstraZeneca at 18 sites in 4 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 7 inclusion and 11 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: stopped early, as of the sponsor's last update on 1 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Czechia, Poland, Bulgaria, United Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was stopped early (reason given: Attendance at study sites carries risk of COVID-19 infection. Non-attendance at planned study site visits has unacceptable study related patient safety risk.). Results are not available in the source record.
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?
Relative change (%) from baseline in serum potassium (time frame: Measurements on day 1, 7, 14, 21 and 28 will be used. The primary comparison between Spironolactone and AZD9977 will be done at day 28.). 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 1 May 2020; AzTrials last refreshed its copy on 7 Nov 2026.