Water PET MPI for Coronary Heart Disease

(RAPID-WATER Trial)

Recruiting at 10 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

Trial Summary

What is the purpose of this trial?

This a Phase 3, prospective, open-label, multicenter study of \[15-O\]-H2O injection for PET imaging of subjects with suspected CAD. Approximately 182 evaluable participants with suspected CAD referred for testing will be included in the study at approximately 10 study sites in the United States and Europe. Approximately 215 participants will be enrolled to account for an estimated 15% drop-out rate. Screening assessments will occur prior to enrollment to confirm eligibility. All participants 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). A safety follow-up phone call will occur 24 ± 8 hrs after completion of the \[15-O\]-H2O scan.

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 data supports the effectiveness of the treatment [O-15]-Water PET Cardiac Perfusion Imaging for coronary heart disease?

Research shows that [O-15]-Water PET Cardiac Perfusion Imaging can help predict the need for procedures like coronary angiography and revascularization in patients with coronary artery disease, indicating its usefulness in guiding treatment decisions. ^{1 2 3 4 5}

Is [O-15]-Water PET MPI safe for humans?

The use of [O-15]-Water PET for imaging has been around for a long time and is considered safe for humans. The short half-life of the oxygen-15 isotope used in the imaging process means it doesn't stay in the body for long, which helps ensure safety. ^{1 2 6 7 8}

How does the Water PET MPI treatment differ from other treatments for coronary heart disease?

Water PET MPI uses a special imaging technique with oxygen-15-labeled water to measure blood flow in the heart, helping doctors decide if invasive procedures are needed. This approach is unique because it provides detailed, quantitative information about heart blood flow, which can guide treatment decisions more precisely than some other imaging methods. ^{1 2 5 7 9}

Research Team

Nicholas Borys, MD

Principal Investigator

MedTrace Pharma A/S

Marcelo DiCarli, MD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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]

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]

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]

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]

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]

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]

References

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

Extracardiac findings with increased perfusion during clinical O-15-H2O PET/CT myocardial perfusion imaging: A case series. [2023]

2. United States 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. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Myocardial perfusion imaging with 13N-ammonia PET is a strong predictor for outcome. [2022]

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

Women with high exercise tolerance and the role of myocardial perfusion imaging. [2020]

5. England 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Validation protocol for current good manufacturing practices production of [15O]water for hybrid PET/MR studies. [2021]

7. Iran pubmed.ncbi.nlm.nih.gov

Association between Cardiovascular Risk Factors and High-Risk Features in Myocardial Perfusion Imaging: A Multicenter Study. [2023]

8. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

[Normal and Near Normal Myocardial Perfusion Imaging Data Analysis: Two-Year Major Adverse Cardiac Event]. [2022]

9. United States 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. [2020]