Water PET MPI for Coronary Heart Disease

(RAPID-WATER Trial)

Recruiting at 15 trial locations

Overseen By Laurel Sindelar (North America)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: MedTrace Pharma A/S

Must not be taking: PDE5 inhibitors

Disqualifiers: Cardiac disease, Severe COPD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

215 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new imaging method using a special water-based PET scan to better detect coronary artery disease (CAD). Participants with suspected CAD receive two doses of a radioactive tracer, one at rest and one during stress, to help doctors see how blood flows to the heart. This method could improve diagnosis and treatment plans for heart-related issues. Suitable candidates include those referred for heart testing who have not undergone major heart interventions. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking diagnostic advancement.

Will I have to stop taking my current medications?

The trial requires that you stop taking sildenafil (Viagra), oral dipyridamole (Persantine, Aggrenox), or any PDE5 inhibitors (like tadalafil, avanafil, vardenafil) at least 24 hours before the study treatment. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

What prior data suggests that [O-15]-Water PET Myocardial Perfusion Imaging (MPI) is safe for humans?

Research has shown that [O-15]-Water PET imaging is generally safe and well-tolerated. This imaging method effectively measures blood flow in the heart, aiding doctors in assessing heart health. Studies indicate that it provides accurate results with very low radiation exposure, making it safe for use. It has been utilized in other studies to evaluate heart conditions. For any concerns, discussing them with a doctor is advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about [O-15]-Water PET Myocardial Perfusion Imaging (MPI) because it offers a unique way to assess coronary heart disease. Unlike traditional imaging methods like SPECT, which use different radioactive tracers, this technique utilizes [O-15]-water, providing a more precise and detailed view of heart blood flow. This improved accuracy can lead to better diagnosis and management of coronary artery disease. Furthermore, the use of [O-15]-water allows for quicker imaging sessions, which can be more comfortable for patients and may lead to faster clinical decision-making.

What evidence suggests that this imaging technique is effective for coronary heart disease?

Research has shown that [O-15]-Water PET Myocardial Perfusion Imaging (MPI), which participants in this trial will receive, effectively diagnoses coronary artery disease (CAD). This imaging technique assesses blood flow in the heart muscles, crucial for identifying heart issues. Studies have found it plays a key role in determining whether patients require more invasive heart procedures. It also helps predict the need for coronary catheterization, a detailed examination of the heart's blood vessels. Overall, this method is a proven and reliable tool in heart imaging. ^{1 2 6 7 8}

Who Is on the Research Team?

Nicholas Borys, MD

Principal Investigator

MedTrace Pharma A/S

Marcelo DiCarli, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

Adults referred for coronary artery disease (CAD) testing, who can undergo PET imaging and are not pregnant or breastfeeding. They must agree to use contraception and have had recent non-invasive CAD tests or invasive angiography with minimal findings. Excluded are those with significant heart disease history, severe lung conditions, certain medication usage, or involvement in other drug trials.

Inclusion Criteria

I had a heart scan that showed either no issues or very minor artery problems.

I will use birth control until the study ends.

I am not pregnant or breastfeeding and am using birth control.

Exclusion Criteria

Participants who have participated in another research study using investigational drugs within the 30 days prior to enrollment or through the duration of the trial

You are not able to have any of the required imaging tests.

I have a history of heart disease or issues like a heart attack or weak heart muscle.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

PET Imaging Session

Participants receive two doses of [15-O]-H2O for PET imaging, one at rest and one during pharmacological stress with adenosine

1 day

1 visit (in-person)

Safety Follow-up

A safety follow-up phone call occurs 24 ± 8 hours after the PET imaging session

1 day

1 call (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

What Are the Treatments Tested in This Trial?

Interventions

• [O-15]-Water PET Cardiac Perfusion Imaging
• [O-15]-Water PET Myocardial Perfusion Imaging (MPI)

Trial Overview [O-15]-Water PET Myocardial Perfusion Imaging is being tested on participants with suspected CAD. The study involves two doses of [15-O]-H2O during a single PET scan session under rest and stress conditions induced by adenosine at multiple sites in the US and Europe.

How Is the Trial Designed?

Group I: [O-15]-Water PET Myocardial Perfusion Imaging (MPI) Experimental Treatment 1 Intervention

All participants with suspected CAD will receive two doses of \[15-O\]-H2O as part of a single PET imaging session (one dose at rest and one during pharmacological stress with adenosine).

Who Is Running the Clinical Trial?

MedTrace Pharma A/S

Lead Sponsor

Trials

1

Recruited

220+

Published Research Related to This Trial

In a study of 2963 patients using O-15-H2O PET myocardial perfusion imaging (MPI), significant extracardiac findings were identified, including various malignant tumors and benign conditions, indicating the method's potential for detecting additional health issues beyond cardiac assessment.

The study suggests that evaluating summed O-15-H2O PET images alongside low-dose CT attenuation images can enhance the detection of these extracardiac findings, highlighting the importance of comprehensive imaging in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extracardiac findings with increased perfusion during clinical O-15-H2O PET/CT myocardial perfusion imaging: A case series. Jochumsen, MR., Overgaard, DL., Vendelbo, MH., et al.[2023]

In a study of 172 symptomatic patients with previous coronary artery bypass grafts (CABG), 15O-H2O myocardial perfusion imaging (MPI) was found to effectively predict which patients would experience relief from angina after undergoing percutaneous coronary intervention (PCI), with a high accuracy indicated by area under the curve (AUC) values of 0.85 and 0.90 for global and vessel-specific myocardial blood flow (MBF) respectively.

While MPI could not predict which patients would be referred for coronary angiography (CAG), it did show that lower vessel-specific MBF and myocardial flow reserve (MFR) values were associated with a higher likelihood of undergoing PCI, suggesting that these parameters can guide treatment decisions for CABG patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myocardial perfusion imaging by 15O-H2O positron emission tomography predicts clinical revascularization procedures in symptomatic patients with previous coronary artery bypass graft. Vester, M., Madsen, S., Kjærulff, MLG., et al.[2023]

In a study of 943 patients using (13)N-ammonia PET for myocardial perfusion imaging, abnormal perfusion was linked to a significantly higher risk of major adverse cardiac events (MACE) and hard events like cardiac death and non-fatal myocardial infarction over a follow-up period of approximately 5.7 years.

The findings suggest that myocardial perfusion imaging with (13)N-ammonia PET is a strong long-term predictor of cardiac outcomes, highlighting its potential value in assessing patients with suspected myocardial perfusion abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myocardial perfusion imaging with 13N-ammonia PET is a strong predictor for outcome. Fiechter, M., Gebhard, C., Ghadri, JR., et al.[2022]

In a study of 57 patients using oxygen-15-labeled water PET/CT myocardial perfusion imaging, those with abnormal results had a significantly higher referral rate for invasive coronary angiography (ICA) (48.7%) compared to those with normal results (5.6%).

Hyperemic myocardial blood flow (MBF) was identified as a strong predictor for both referral to ICA and subsequent revascularization, indicating that this imaging technique can effectively guide clinical decision-making in managing coronary artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical impact of quantitative [15O] H2O PET/CT myocardial perfusion imaging on decision-making regarding invasive management of coronary artery disease. Promteangtrong, C., Jantarato, A., Kunawudhi, A., et al.[2022]

In a study of 4886 patients, 44.6% had abnormal myocardial perfusion imaging (MPI), with older age and common risk factors like diabetes, hypertension, and dyslipidemia significantly linked to these abnormal results.

The likelihood of having an abnormal MPI increased dramatically with the number of CAD risk factors, from just 3.7% in patients with one or no risk factors to 76.2% in those with eight risk factors, highlighting the importance of careful evaluation in at-risk individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between Cardiovascular Risk Factors and High-Risk Features in Myocardial Perfusion Imaging: A Multicenter Study. Khederlou, H., Mohammadi, A., Tajik, M., et al.[2023]

A new two-vial production method for [O]water was developed, ensuring consistent yields of 10-12 GBq shortly after production, which is crucial for safe and effective nuclear imaging in clinical studies.

Quality control testing of 26 batches confirmed that all met safety and efficacy standards, making this protocol a reliable option for facilities producing [O]water for patient use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation protocol for current good manufacturing practices production of [15O]water for hybrid PET/MR studies. Cockburn, N., Corsaut, J., Kovacs, MS., et al.[2021]

Myocardial perfusion imaging (MPI) can effectively predict cardiac events in patients with chronic kidney disease (CKD), as demonstrated in a study of 529 CKD patients over 3 years, where higher MPI scores were linked to increased risk of cardiac issues.

Key risk factors identified include an eGFR of less than 15 mL/minute/1.73 m² and CRP levels of 0.3 mg/dL or higher, indicating that MPI, along with these markers, can help in assessing the risk of cardiac events in CKD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic study of cardiac events in Japanese patients with chronic kidney disease using ECG-gated myocardial Perfusion imaging: Final 3-year report of the J-ACCESS 3 study. Nakamura, S., Kawano, Y., Nakajima, K., et al.[2020]

In a study of 1,629 patients with normal or near-normal myocardial perfusion imaging (MPI) results, 15.8% of those with normal results and 16.6% with near-normal results experienced major adverse cardiac events (MACE) over a two-year follow-up period.

Key risk factors for MACE included older age, male gender, and poor myocardial perfusion parameters, highlighting the importance of patient education on managing these risks, such as controlling hyperlipidemia and monitoring left ventricular ejection fraction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Normal and Near Normal Myocardial Perfusion Imaging Data Analysis: Two-Year Major Adverse Cardiac Event]. Tang, LH., Huang, YH., Chen, CJ., et al.[2022]

In a study of 311 women with high exercise tolerance who underwent myocardial perfusion imaging (MPI), only 7.4% had abnormal results, indicating that MPI may have limited diagnostic value in this population.

The study found that women with high exercise tolerance, particularly those without known coronary artery disease (CAD), have an excellent prognosis, with no myocardial infarctions or cardiac deaths occurring within 3 years of follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Women with high exercise tolerance and the role of myocardial perfusion imaging. Chatziioannou, SN., Moore, WH., Dhekne, RD., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33826128/

Clinical impact of quantitative [ 15 O] H 2 O PET/CT ... [ 15 O] H 2 O PET/CT MPI showed a clinical impact on decision-making regarding invasive procedure for management of CAD.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1071358124006871

PET myocardial perfusion imaging: Trends, challenges ... This state-of-art review focuses on quantitative PET MPI, its integration into clinical practice, and how it holds up at the eyes of modern cardiac imaging and ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32284110/

15O-Water PET MPI: Current Status and Future Perspectives 15O-water positron emission tomography (PET) is a validated tool for quantitative measurement of myocardial blood flow (MBF) and myocardial flow reserve (MFR).

4. academic.oup.com academic.oup.com/ehjopen/article/3/3/oead044/7146402

Myocardial perfusion imaging by 15O-H2O positron emission ... We wanted to assess if 15 OH 2 O myocardial perfusion imaging (MPI) in a clinical setting can predict referral to coronary artery catheterization.

5. researchgate.net researchgate.net/publication/304342625_Computed_tomography_myocardial_perfusion_vs_15O-water_positron_emission_tomography_and_fractional_flow_reserve

Computed tomography myocardial perfusion vs 15O-water ... We compared CT coronary angiography (CTCA) and CT myocardial perfusion (CTP) with (15)O-water positron emission tomography (PET) and invasive ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01805193

NCT01805193 | Myocardial Blood Flow by 15O Water PET Suspected coronary heart disease, Intervention/Treatment, Other : Computed tomography myocardial perfusion imaging. Other : Oxygen 15 labelled water positron ...

7. heart.org heart.org/en/health-topics/heart-attack/diagnosing-a-heart-attack/myocardial-perfusion-imaging

Myocardial Perfusion Imaging Test: PET and SPECT Myocardial perfusion imaging (MPI) is a test that shows how well blood flows through the heart muscle. There are two kinds of MPI: PET scan ...

8. medtracepharma.com medtracepharma.com/science/

Understanding ¹⁵O-Water The Next Step in PET Imaging Discover how ¹⁵O-Water, a revolutionary tracer, enhances PET imaging accuracy in diagnosing heart disease with minimal patient radiation exposure.