Remote Ischemic Preconditioning for Heart Failure

(RICH Trial)

Recruiting at 2 trial locations

Overseen By Oladipupo Olafiranye, MD MS

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: VA Office of Research and Development

Disqualifiers: Unstable BP, Kidney transplant, Pregnancy, others

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: Immediate (during procedure)

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a technique called remote ischemic preconditioning to determine its effectiveness for people with heart failure undergoing procedures like cardiac catheterization. The goal is to assess whether this technique can protect the kidneys and enhance overall heart and kidney function. Participants will undergo cycles of blood pressure cuff inflations, either to a high pressure or to a lower, more comfortable pressure, which serves as a control. Ideal participants have heart failure with reduced heart pumping ability and are preparing for heart-related procedures. As a Phase 2/3 trial, this study measures the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in heart failure treatment.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that remote ischemic preconditioning (RIPC) is generally safe and well-tolerated. This technique uses a blood pressure cuff that inflates and deflates in cycles to help protect organs during medical procedures. Studies suggest that RIPC can lower the risk of complications like heart attacks and strokes and may aid in recovery after heart-related events.

Previous studies have reported no major serious side effects from RIPC. Most participants handle the treatment well, experiencing few negative effects. The trial's progression to later stages indicates that earlier trials found the treatment safe enough for broader testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Remote ischemic preconditioning is unique because it leverages the body's natural protective responses by temporarily stopping and then restoring blood flow, which may help the heart become more resilient to stress. Unlike standard heart failure treatments, which often focus on managing symptoms with medications like beta-blockers or ACE inhibitors, this approach uses cycles of blood pressure cuff inflation to potentially improve heart function. Researchers are excited about this technique because it offers a non-invasive way to enhance heart health and could serve as a complementary method alongside traditional therapies.

What evidence suggests that remote ischemic preconditioning is effective for heart failure?

Research has shown that remote ischemic preconditioning (RIPC), which participants in this trial may receive, can help reduce heart problems. Some studies indicate that RIPC decreases the size of heart attacks in individuals experiencing an acute myocardial infarction, a type of heart attack. In those with mild heart failure, RIPC has improved heart function, aiding the heart in pumping blood more effectively. Another study found that RIPC reduces the risk of kidney issues after heart procedures. These findings suggest that RIPC might benefit heart and kidney health in certain situations. ^{1 2 6 7 8}

Who Is on the Research Team?

Oladipupo Olafiranye, MD MS

Principal Investigator

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Are You a Good Fit for This Trial?

The RICH trial is for adults over 18 with heart failure (LVEF <50%) and suspected coronary artery disease, who are referred for a coronary angiogram or PCI. They should have a risk of kidney injury from the procedure and not be on certain pre-procedure fluids. Excluded are those unable to consent, with extreme blood pressure, on dialysis, pregnant, prisoners, with arm arterial disease or recent contrast media exposure.

Inclusion Criteria

You have a high risk of developing acute kidney injury according to the SCAI score.

I am referred for a procedure to check or unblock my heart's arteries.

I may have stable heart disease or a recent heart problem.

Exclusion Criteria

I require dialysis for my kidney condition.

I have had a kidney transplant.

Your blood pressure is very high (over 200) or very low (under 80) when you join the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo remote ischemic preconditioning or sham procedure during cardiac catheterization and/or percutaneous coronary intervention

Immediate (during procedure)

1 visit (in-person)

Initial Follow-up

Participants are monitored for contrast-associated acute kidney injury with serum creatinine levels measured at 24 and 48 hours post-procedure

48 hours

2 visits (in-person)

Secondary Follow-up

Participants' functional capacity assessed with a 6-minute walk test at one month

1 month

1 visit (in-person)

Long-term Follow-up

Participants are monitored for major adverse kidney events at 3 months

3 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Remote ischemic preconditioning
• Sham remote ischemic conditioning

Trial Overview This study tests whether remote ischemic preconditioning can protect kidneys and heart in patients with congestive heart failure undergoing cardiac procedures. Participants will be randomly assigned to receive either the actual preconditioning technique or a sham (fake) intervention without knowing which one they get.

How Is the Trial Designed?

Group I: Remote ischemic preconditioning Active Control 1 Intervention

3 cycles of blood pressure cuff inflations to occlusive pressure of 200 mmHg for 5 minutes and deflation for 5 minutes

Group II: Sham remote ischemic preconditioning Placebo Group 1 Intervention

3 cycles of blood pressure cuff inflations to non-occlusive pressure of 60 mmHg for 5 minutes and deflation for 5 minutes (Control)

Remote ischemic preconditioning is already approved in European Union, United States for the following indications:

Approved in European Union as Remote ischemic preconditioning for:

• Cardiac protection in children undergoing open-heart surgery
• Renal protection in patients undergoing cardiac catheterization and/or percutaneous coronary intervention

Approved in United States as Remote ischemic preconditioning for:

• Cardiac protection in patients undergoing open-heart surgery
• Renal protection in patients undergoing cardiac catheterization and/or percutaneous coronary intervention

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

Remote ischemic preconditioning (rIPC) protects the heart from injury during ischemia/reperfusion (I/R) by utilizing circulating nitrite, which is produced from nitric oxide during reactive hyperemia in a remote site, such as the femoral artery.

Inhibition of nitric oxide production or its activation in the heart negates the cardioprotective effects of rIPC, highlighting the critical role of nitrite in reducing heart damage and improving outcomes during I/R events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating nitrite contributes to cardioprotection by remote ischemic preconditioning. Rassaf, T., Totzeck, M., Hendgen-Cotta, UB., et al.[2022]

Remote ischaemic preconditioning (RIPC) significantly improved walking distances in people with multiple sclerosis, with a 5.7% increase in the Six-Minute Walk Test compared to only 1.9% in the sham group, indicating its potential efficacy as a therapeutic intervention.

The study involved 75 participants and found that RIPC not only enhanced walking performance but also had no serious adverse events, suggesting it is a safe and tolerable treatment option for improving mobility in MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of remote ischaemic preconditioning on walking in people with multiple sclerosis: double-blind randomised controlled trial. Chotiyarnwong, C., Nair, K., Angelini, L., et al.[2022]

Remote ischemic preconditioning (RIPC) is a safe technique for patients undergoing on-pump coronary artery bypass grafting (CABG), with no reported cases of limb ischemia or nerve damage during the procedure.

However, RIPC does not provide additional clinical benefits in terms of myocardial injury or postoperative outcomes compared to standard myocardial protection strategies, as shown by similar levels of cardiac injury markers and postoperative complications between the RIPC and non-RIPC groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote ischemic preconditioning is a safe adjuvant technique to myocardial protection but adds no clinical benefit after on-pump coronary artery bypass grafting. Ahmad, AM., Ali, GS., Tariq, W.[2022]

In a study involving 75 patients with stable coronary artery disease, remote ischaemic preconditioning (RIPC) significantly reduced vasoconstriction in response to acetylcholine, suggesting it enhances coronary vasodilation through an endothelium-dependent mechanism.

The RIPC group showed a mean percentage change in coronary luminal diameter of -2.0%, compared to -13.3% in the sham group, indicating a protective effect of RIPC on coronary blood flow during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of remote ischaemic preconditioning on coronary artery function in patients with stable coronary artery disease. Corcoran, D., Young, R., Cialdella, P., et al.[2021]

In a study involving 42 patients with single vessel coronary disease, remote ischaemic pre-conditioning (RIPC) did not reduce the level of left ventricular (LV) dysfunction during coronary occlusion, indicating it may not be effective in protecting the heart from ischaemic injury.

RIPC also failed to improve contractile recovery of the heart after reperfusion, suggesting that this intervention does not enhance LV function in patients experiencing ischaemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote ischaemic pre-conditioning does not attenuate ischaemic left ventricular dysfunction in humans. Hoole, SP., Khan, SN., White, PA., et al.[2016]

In a study involving 1403 patients undergoing elective cardiac surgery, remote ischemic preconditioning (RIPC) did not significantly reduce the rates of major complications such as death, myocardial infarction, stroke, or acute renal failure compared to a sham intervention.

No adverse events related to RIPC were reported, indicating that while RIPC may not provide clinical benefits, it is a safe procedure when performed under anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery. Meybohm, P., Bein, B., Brosteanu, O., et al.[2022]

Recent phase III studies, RIPHeart and ERICCA, have been conducted to evaluate the clinical benefits of remote ischaemic preconditioning (RIPC) in patients undergoing heart surgery, addressing the need for evidence in clinical practice.

The outcomes of these studies are crucial for determining whether RIPC can be recommended as a standard cardioprotective strategy, following promising results from earlier animal and phase II human studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote preconditioning and cardiac surgery: regrouping after Remote Ischemic Preconditioning for Heart Surgery (RIPHeart) and Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Surgery (ERICCA). Cheung, CX., Healy, DA., Walsh, SR.[2020]

Remote ischaemic preconditioning (RIPC) does not significantly alter the levels of inflammatory cytokines (IL-6, IL-8, IL-10) in patients undergoing high-risk cardiac surgery, indicating that its cardioprotective effects may not be mediated through changes in these cytokines.

Despite RIPC not affecting cytokine levels, high levels of IL-6 and IL-10 were observed during surgery, particularly in complex procedures, suggesting that further research is needed to understand the mechanisms behind RIPC and its potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote ischaemic preconditioning does not alter perioperative cytokine production in high-risk cardiac surgery. Williams, JM., Young, P., Pilcher, J., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7169952/

Chronic remote ischemic conditioning for cardiovascular ... Remote ischemic conditioning (RIC) using transient limb ischemia and reperfusion has been reported to reduce myocardial infarct (MI) size in AMI patients ...

2. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.075254

The PRINCE Randomized Clinical Trial | Circulation Remote ischemic preconditioning (RIPC) was reported to decrease these complication rates. However, such supportive evidence lacks robustness.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11349135/

Remote Ischemic Conditioning Improves Cardiovascular ... They reported that 6 weeks of RIC treatment improved heart function in patients with mild ischemic heart failure, leading to increases in LVEF (from 39.2% to ...

4. acc.org acc.org/Latest-in-Cardiology/Journal-Scans/2025/03/19/12/07/Remote-Ischemic-Preconditioning

Remote Ischemic Preconditioning Lowers AKI Incidence ... Results showed that the incidence of CA-AKI was lower with delayed vs. sham RIPC (3.2% vs. 7.6%; odds ratio, 0.40; p=0.03). Looking at secondary ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1413579

A Multicenter Trial of Remote Ischemic Preconditioning for ... Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3286899/

Clinical Applications of Remote Ischemic Preconditioning Remote ischemic preconditioning refers to a stimulus applied to a distant organ or tissue, which then protects against index ischemia.

7. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.123.043279

Remote Ischemic Conditioning: Challenges and ... It has been found that the protection of once ischemic preconditioning can last for ≈96 hours, with a 12–24 hours interval of no protection.

8. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-023-04786-y

Remote ischemic conditioning reduces adverse events in ... Treatment with remote ischemic conditioning decreased the major adverse cardiac and cerebrovascular events and improved functional outcomes at 90 days.