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

Trial Summary

What is the purpose of this trial?

This is a prospective, double-blind, sham-controlled, multicenter, randomized clinical trial is to study the effects of remote ischemic preconditioning on contrast-associated acute kidney injury, functional capacity, and major adverse kidney events in in patients with congestive heart failure undergoing cardiac catheterization and/or percutaneous coronary intervention.

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.

What data supports the effectiveness of the treatment Remote Ischemic Preconditioning for Heart Failure?

Research shows that Remote Ischemic Preconditioning (RIPC) can reduce markers of heart damage during surgery, but its impact on overall health outcomes is still uncertain. While it is considered safe, studies have not yet proven significant clinical benefits for heart surgery patients. ^{1 2 3 4 5}

How is the treatment Remote Ischemic Preconditioning (RIPC) unique for heart failure?

Remote Ischemic Preconditioning (RIPC) is unique because it involves applying brief periods of reduced blood flow to a part of the body away from the heart, which can help protect the heart from damage. Unlike traditional treatments that directly target the heart, RIPC uses this indirect method to potentially improve heart function and outcomes. ^{1 4 6 7 8}

Research Team

Oladipupo Olafiranye, MD MS

Principal Investigator

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

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. China 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). [2020]

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

A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Remote ischaemic preconditioning does not alter perioperative cytokine production in high-risk cardiac surgery. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The effects of remote ischaemic preconditioning on coronary artery function in patients with stable coronary artery disease. [2021]

5. United States 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. [2022]

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

Circulating nitrite contributes to cardioprotection by remote ischemic preconditioning. [2022]

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

Remote ischaemic pre-conditioning does not attenuate ischaemic left ventricular dysfunction in humans. [2016]

8. England pubmed.ncbi.nlm.nih.gov

Effect of remote ischaemic preconditioning on walking in people with multiple sclerosis: double-blind randomised controlled trial. [2022]