AZD0780 for Cardiovascular Disease

(AZD0780-ABPM Trial)

Recruiting at 25 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: AstraZeneca

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a Phase II, multi-centre, randomized, double-blind, placebo-controlled, crossover study to evaluate the effect of AZD0780 Dose 1 versus placebo on systolic blood pressure (SBP) at Week 4, as measured by 24-hour ambulatory blood pressure monitoring (ABPM) in participants with ASCVD or risk equivalents and LDL-C ≥ 70 mg/dL, on stable medication.

Do I have to stop taking my current medications for the trial?

No, you don't have to stop taking your current medications. Participants must be on stable medication for at least 4 weeks before the trial and should not change their medication or dose during the study.

What data supports the idea that AZD0780 for Cardiovascular Disease is an effective treatment?

The available research does not provide any data specifically about AZD0780 for Cardiovascular Disease. Instead, the studies focus on the use of left ventricular assist devices (LVADs) for heart failure, showing that LVADs can improve survival and quality of life compared to medical management. There is no information on AZD0780's effectiveness for cardiovascular disease in the provided research. ^{1 2 3 4 5}

What safety data is available for AZD0780 in treating cardiovascular disease?

The provided research does not contain specific safety data for AZD0780 in treating cardiovascular disease. The studies focus on other treatments and conditions, such as cilostazol for peripheral arterial disease and beta agonists for COPD, as well as general cardiovascular event rates in claudication trials. Therefore, no direct safety data for AZD0780 is available from these sources. ^{6 7 8 9 10}

Is the drug AZD0780 a promising treatment for cardiovascular disease?

The information provided does not directly mention AZD0780 or its effects on cardiovascular disease. Therefore, we cannot determine if AZD0780 is a promising treatment based on the given research articles. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for people with cardiovascular disease or atherosclerosis and LDL cholesterol levels of 70 mg/dL or higher, who are on stable medication. Participants should be willing to have their blood pressure monitored for 24 hours.

Inclusion Criteria

Body mass index ≥ 19.0 kg/m2.

I am a male or a female not able to have children.

My current medications for other health issues have been stable for at least 4 weeks.

Exclusion Criteria

I had heart bypass surgery within the last 6 months or a heart stent placed within the last 3 months.

I have no conditions that affect how my body handles medicine.

My diabetes is not well-managed, with an HbA1c level over 10%.

Treatment Details

Interventions

• AZD0780 (Other)

Trial Overview The study tests the effect of AZD0780 compared to a placebo on systolic blood pressure after four weeks. It's a Phase II trial where participants will receive either the drug or placebo randomly and then switch, without knowing which one they're taking.

Participant Groups

Group I: AZD0780 Experimental Treatment 1 Intervention

Following randomization to treatment sequence, participants receive AZD0780 during period 1 or 2.

Group II: Placebo Placebo Group 1 Intervention

Following randomization to treatment sequence, participants receive Placebo during period 1 or 2.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Fortrea

Industry Sponsor

Trials

22

Recruited

5,800+

Findings from Research

In a study of 159 patients who underwent cardiovascular implantable electronic device (CIED) surgery after receiving a left ventricular assist device (LVAD), there was a notable risk of complications, including a 13.2% incidence of pocket hematoma and a 3.1% rate of device infection, primarily linked to those who experienced hematomas.

The 1-year mortality rate following CIED surgery in these patients was 20%, highlighting the need for careful consideration of the risks versus benefits of such procedures in individuals with LVADs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Implantable Electronic Device Surgery Following Left Ventricular Assist Device Implantation. Black-Maier, E., Lewis, RK., Loungani, R., et al.[2022]

In the ROADMAP study, patients with advanced heart failure who received a left ventricular assist device (LVAD) showed significant improvements in health-related quality of life (hrQoL) compared to those receiving optimal medical management, particularly in patients with low baseline quality of life scores (VAS < 55).

Patients with low baseline hrQoL (VAS < 55) had better survival rates on LVAD therapy (82%) compared to those on optimal medical management (58%), highlighting the importance of assessing hrQoL when considering LVAD implantation for heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Reported Health-Related Quality of Life Is a Predictor of Outcomes in Ambulatory Heart Failure Patients Treated With Left Ventricular Assist Device Compared With Medical Management: Results From the ROADMAP Study (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management). Stehlik, J., Estep, JD., Selzman, CH., et al.[2018]

Implanted left ventricular assist devices (LVADs) are increasingly used as an alternative treatment for patients with advanced heart failure, especially given the shortage of donor organs for heart transplantation.

This umbrella review aims to evaluate the impact of LVADs on patients' quality of life, survival rates, and functional classification, providing essential information for clinicians and patients regarding treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life in patients with advanced heart failure and an implanted left ventricular assist device: an umbrella review protocol. Abrams, D., McNair, M.[2023]

Patients with INTERMACS Profile 4 who received left ventricular assist device (LVAD) therapy showed significantly better outcomes, with 40% meeting the primary endpoint of improved walking distance compared to only 15% in those receiving optimal medical management (OMM).

While LVAD therapy improved event-free survival and quality of life in Profile 4 patients, it did not show the same benefits for Profiles 5 to 7, suggesting that LVAD may be more beneficial for select patients in Profile 4, despite a higher incidence of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left ventricular assist devices versus medical management in ambulatory heart failure patients: An analysis of INTERMACS Profiles 4 and 5 to 7 from the ROADMAP study. Shah, KB., Starling, RC., Rogers, JG., et al.[2019]

The National Heart, Lung, and Blood Institute (NHLBI) is exploring the use of ventricular assist devices (VADs) in less severely ill heart failure patients, aiming to improve survival and quality of life for those not yet facing serious complications.

The REVIVE-IT Pilot Trial, initiated based on recommendations from a working group, will assess the effectiveness of chronic VAD therapy in moderately advanced heart failure patients, potentially expanding the eligibility for VADs beyond late-stage cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NHLBI's program for VAD therapy for moderately advanced heart failure: the REVIVE-IT pilot trial. Baldwin, JT., Mann, DL.[2021]

In a study analyzing the electronic medical records of 1.8 million patients over 18 years, Cilostazol use in 232 patients with peripheral arterial disease (PAD) showed no significant association with major adverse cardiovascular events, including stroke, heart attack, or death, over a mean follow-up of 4.2 years.

Cilostazol did not increase mortality in a subset of high-risk patients with congestive heart failure (CHF), suggesting that the black box warning regarding cardiovascular mortality may be unnecessarily limiting its use as an effective treatment for intermittent claudication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practice-based evidence: profiling the safety of cilostazol by text-mining of clinical notes. Leeper, NJ., Bauer-Mehren, A., Iyer, SV., et al.[2023]

In clinical trials for patients with claudication, the mortality rate was found to be 1.9 deaths per hundred patient-years, which is lower than rates reported in natural history studies, indicating a relatively safer profile for participants in these trials.

Cardiovascular serious adverse events occurred at a rate of 8.5 per hundred patient-years, highlighting the need for careful monitoring of cardiovascular health in claudication trials and providing important benchmarks for future safety assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of mortality and cardiovascular event rates in patients enrolled in clinical trials for claudication therapies. Brass, EP., Hiatt, WR.[2017]

In a study of over 1.4 million patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD), those with one or more risk factors (like diabetes or heart failure) had significantly higher risks of major adverse cardiovascular events (MACEs), with a 72% increased hazard compared to low-risk patients.

Patients with multiple risk factors also faced a 146% higher hazard of major adverse limb events (MALEs) and an 82% higher hazard of major thrombotic vascular events, highlighting the critical need for better management of these underlying conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Incidence of Adverse Clinical Outcomes Among People With Coronary Artery Disease and/or Peripheral Artery Disease in Relation to Vascular Risk in the United States. Desai, U., Babcock, A., Wang, Y., et al.[2023]

In a 3-year study involving 6184 patients with moderate to severe COPD, the long-acting beta(2) agonist salmeterol did not increase the risk of cardiovascular adverse events compared to placebo or other treatments.

The rates of cardiovascular events were similar across all treatment groups, indicating that salmeterol, whether used alone or in combination with fluticasone propionate, is safe for patients with COPD regarding cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular events in patients with COPD: TORCH study results. Calverley, PM., Anderson, JA., Celli, B., et al.[2022]

Patients with peripheral artery disease (PAD) who experienced a myocardial infarction (MI) had a significantly higher risk of major adverse cardiovascular events (MACE) within one year compared to those without PAD, with a relative risk of 1.21.

The study, which included over 179,000 patients, found that PAD was associated with increased risks of all-cause mortality, cardiovascular mortality, reinfarction, stroke, heart failure, and bleeding episodes, highlighting the need for better diagnosis and management of PAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of peripheral artery disease on major adverse cardiovascular events following myocardial infarction. Andersen, P., Kragholm, K., Torp-Pedersen, C., et al.[2021]

In a study using transverse aortic constriction (TAC) in adult male mice, varying degrees of constriction (25G, 26G, and 27G) resulted in different levels of cardiac hypertrophy and dysfunction, indicating that the severity of TAC directly influences heart health outcomes.

Mice with the most severe constriction (27G) showed significant systolic and diastolic dysfunction, severe cardiac fibrosis, and signs of heart failure, while those with moderate constriction (26G) exhibited milder dysfunction, suggesting that these models can be tailored for specific research needs in studying heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distinct Phenotypes Induced by Three Degrees of Transverse Aortic Constriction in Mice. Richards, DA., Aronovitz, MJ., Calamaras, TD., et al.[2021]

Serum levels of Zinc-α2-glycoprotein (AZGP1) were found to be significantly lower in patients with coronary heart disease (CHD) compared to controls, suggesting that AZGP1 may play a protective role against CHD.

AZGP1 exhibits anti-inflammatory properties by regulating JNK/AP-1 signaling, indicating its potential as a therapeutic target for treating CHD and atherosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of adipokine zinc-&#945;2-glycoprotein in coronary heart disease. Huang, D., Mao, X., Peng, J., et al.[2020]

In a study involving mice with obesity and insulin resistance induced by a high-fat diet, azilsartan, an angiotensin II receptor blocker, significantly reduced left ventricular wall thickness and hypertrophy, indicating improved heart structure under pressure overload conditions.

Azilsartan also decreased levels of cardiac plasminogen activator inhibitor-1 (PAI-1), a marker of fibrosis, and improved cardiac output, suggesting its potential effectiveness in treating heart failure in obese and insulin-resistant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and tolerability of azilsartan in obese insulin-resistant mice with left ventricular pressure overload. Tarikuz Zaman, AK., McLean, DL., Sobel, BE.[2017]

In a study involving spontaneously hypertensive obese rats treated with azilsartan medoxomil (AZL-M) for 56 days, the drug showed significant anti-hypertensive effects and improved vascular endothelial function.

AZL-M also provided strong protection against kidney and heart damage, evidenced by reduced albuminuria, nephrinuria, and left ventricular hypertrophy, highlighting its potential as a therapeutic option for preventing cardiovascular and renal injury in hypertensive conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azilsartan decreases renal and cardiovascular injury in the spontaneously hypertensive obese rat. Hye Khan, MA., Neckář, J., Cummens, B., et al.[2017]

ZNF418 is significantly down-regulated in cardiac hypertrophy, and its deficiency worsens heart muscle enlargement and fibrosis, indicating its protective role against cardiac hypertrophy.

Overexpression of ZNF418 reduces hypertrophic responses and fibrosis by inhibiting the phosphorylation of c-jun, suggesting a mechanism where ZNF418 may help prevent heart muscle damage in conditions like aortic banding and angiotensin II exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zinc-finger protein 418 overexpression protects against cardiac hypertrophy and fibrosis. Pan, L., Sheng, M., Huang, Z., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cardiovascular Implantable Electronic Device Surgery Following Left Ventricular Assist Device Implantation. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Patient-Reported Health-Related Quality of Life Is a Predictor of Outcomes in Ambulatory Heart Failure Patients Treated With Left Ventricular Assist Device Compared With Medical Management: Results From the ROADMAP Study (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management). [2018]

3. Australia pubmed.ncbi.nlm.nih.gov

Quality of life in patients with advanced heart failure and an implanted left ventricular assist device: an umbrella review protocol. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Left ventricular assist devices versus medical management in ambulatory heart failure patients: An analysis of INTERMACS Profiles 4 and 5 to 7 from the ROADMAP study. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

NHLBI's program for VAD therapy for moderately advanced heart failure: the REVIVE-IT pilot trial. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Practice-based evidence: profiling the safety of cilostazol by text-mining of clinical notes. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Review of mortality and cardiovascular event rates in patients enrolled in clinical trials for claudication therapies. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

Real-World Incidence of Adverse Clinical Outcomes Among People With Coronary Artery Disease and/or Peripheral Artery Disease in Relation to Vascular Risk in the United States. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Cardiovascular events in patients with COPD: TORCH study results. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

The impact of peripheral artery disease on major adverse cardiovascular events following myocardial infarction. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Distinct Phenotypes Induced by Three Degrees of Transverse Aortic Constriction in Mice. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Role of adipokine zinc-&#945;2-glycoprotein in coronary heart disease. [2020]

13. United States pubmed.ncbi.nlm.nih.gov

The efficacy and tolerability of azilsartan in obese insulin-resistant mice with left ventricular pressure overload. [2017]

14. United States pubmed.ncbi.nlm.nih.gov

Azilsartan decreases renal and cardiovascular injury in the spontaneously hypertensive obese rat. [2017]

15. United States pubmed.ncbi.nlm.nih.gov

Zinc-finger protein 418 overexpression protects against cardiac hypertrophy and fibrosis. [2022]