Valve Transplant for Heart Valve Disease

Overseen By Sitaram Emani, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Boston Children's Hospital

Disqualifiers: Morbid obesity, Diabetes, Immunocompromised, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 1-2 weeks

4 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Allogeneic Valve Transplantation for heart valve disease?

The research indicates that allogeneic valve transplantation is an emerging therapy using living valves from donor hearts, with studies exploring its potential use and challenges, such as immune response and contamination risks. While there is evidence of its use in conditions like endocarditis, the effectiveness data for heart valve disease specifically is limited. ^{1 2 3 4 5}

Is valve transplantation generally safe for humans?

Valve transplantation, such as allogeneic valve transplantation, has some safety concerns. There is a rare risk of fungal infection from contaminated valves, which can be serious and sometimes fatal. Additionally, immune system reactions can lead to valve failure, especially in children. ^{1 2 5 6 7}

How is the treatment Allogeneic Valve Transplantation different from other treatments for heart valve disease?

Allogeneic Valve Transplantation is unique because it uses living valves from donor hearts, which can be more durable and self-repairing compared to mechanical or bioprosthetic valves. This treatment also allows patients to avoid the need for lifelong blood-thinning medication, making it particularly beneficial for those who cannot take such medication, like women who wish to become pregnant or people with bleeding disorders. ^{1 6 7 8 9}

What is the purpose of this trial?

Valves will be taken from hearts donated by organ donors, and implanted into patients who need a new heart valve.

Research Team

Sitaram Emani, MD

Principal Investigator

Boston Children's Hospital

Eligibility Criteria

This trial is for patients with various heart valve diseases who require a new heart valve. Participants should need an aortic valve replacement and be suitable candidates for receiving valves from organ donors.

Inclusion Criteria

I need a heart valve replacement.

I have limited options for valve replacement.

Patients at risk of immunogenic bio-prosthetic valve failure

Exclusion Criteria

I have diabetes with complications affecting organs.

I do not have severe genetic, brain, or syndrome-related abnormalities.

I have HIV or chronic hepatitis B or C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo allogeneic valve transplantation

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for valve regurgitation, valve annulus growth, ventricular function, and leaflet growth

1 year

Regular visits (in-person and virtual)

Long-term follow-up

Participants are monitored for survival and long-term outcomes

5 years

Treatment Details

Interventions

• Allogeneic Valve Transplantation

Trial Overview The study involves transplanting heart valves obtained from organ donors into patients with defective or diseased aortic valves, to see if this can effectively treat their condition.

Participant Groups

Group I: Valve transplantation group Experimental Treatment 1 Intervention

This arm undergoes Allogeneic Valve transplantation

Allogeneic Valve Transplantation is already approved in European Union, United States for the following indications:

Approved in European Union as Allogeneic Valve Transplantation for:

• Congenital valve disease
• Infective endocarditis
• Small aortic roots
• Fertile women contemplating pregnancy

Approved in United States as Allogeneic Valve Transplantation for:

• Severe heart failure
• Severe valve dysfunction
• Prosthetic valve infection
• Invasion beyond the valve leaflets
• Recurrent systemic embolization
• Large mobile vegetations
• Persistent sepsis despite adequate antibiotic therapy

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Findings from Research

Out of 72,460 pediatric and young adult heart donations from 1987 to 2022, 43.3% (31,395) were discarded, indicating a significant potential source of valves for allogeneic valve transplantation.

The most common reasons for discarding these hearts included suboptimal graft function and poor organ function, suggesting that improving evaluation and allocation processes could enhance the availability of viable grafts for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in pediatric donor heart discard rates and the potential use of unallocated hearts for allogeneic valve transplantation. Nguyen, SN., Schiazza, A., Richmond, ME., et al.[2023]

Fungal endocarditis, particularly from Candida albicans, is a rare but serious complication of allograft heart valve replacement, occurring in about 0.3% of cases, and often leads to unsuccessful treatment and death.

The investigation revealed that the antimicrobial processing used on the aortic valve allograft failed to completely eliminate C. albicans, highlighting a significant safety concern in the handling of donor tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candida albicans endocarditis associated with a contaminated aortic valve allograft--California, 1996. [2008]

In a study of 10 allograft valves from heart transplant and valve replacement patients, histologic evaluation and DNA analysis revealed that in some heart transplant cases, receptor cells were found mixed with native donor cells, indicating a complex cellular environment.

The findings suggest that understanding the cellular origin of allograft valves could enhance preparation methods, although results for the valve replacement group are still inconclusive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The allograft valve in heart transplantation and valve replacement. Genetic assessment of the origin of the cells by means of deoxyribonucleic acid profiles. Melo, JQ., Monteiro, C., Neves, J., et al.[2006]

In a study involving 32 rats, treatments with cyclosporine and anti-alpha4/beta2 integrin antibodies significantly reduced immune cell infiltration in allograft heart valves, helping to maintain their structural integrity after 7 days.

Long-term treatment with cyclosporine is necessary to prevent valve destruction, as a short 7-day course was insufficient to preserve the valves' integrity after 28 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of allograft heart valve failure in a rat model. Légaré, JF., Ross, DB., Issekutz, TB., et al.[2013]

In a study of 35 adult patients undergoing aortic valve replacement with cryopreserved human aortic valve allografts, those with active endocarditis experienced a higher perioperative mortality rate, with 2 deaths compared to none in the non-infected group, indicating a significant safety concern for infected patients (p<0.05).

Both groups showed no thromboembolic complications or recurrent infections during an average follow-up of 27 to 32 months, suggesting that the surgical techniques used (root-replacement and inclusion techniques) were effective in preventing these issues, regardless of infection status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allograft replacement of the aortic valve for active endocarditis. Ladowski, JS., Deschner, WP.[2016]

Partial heart transplantation is a promising new method for heart valve replacement that could provide durable, self-repairing valves without the need for anticoagulation therapy, making it particularly beneficial for young adults and those with specific health concerns.

This technique allows for the use of donor heart valves, potentially increasing the availability of suitable valves compared to traditional heart transplantation methods, although its clinical effectiveness in adults has yet to be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Partial Heart Transplantation in Adult Cardiac Surgery. Sherard, C., Bisbee, C., Konsek, H., et al.[2023]

In a study involving 24 Lewis rats and 12 T cell-deficient nude rats, allograft heart valves were found to fail due to T cell-mediated immune damage, leading to structural destruction over time.

Syngeneic grafts remained structurally intact with minimal immune response, while allogeneic grafts showed significant immune infiltration and damage, indicating that T cells play a critical role in the rejection of transplanted heart valves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T lymphocytes mediate leaflet destruction and allograft aortic valve failure in rats. Legare, JF., Lee, TD., Creaser, K., et al.[2019]

Aortic valve replacement with human allograft valves shows a host-graft interaction that varies based on the sterilizing and storage methods used before implantation.

A new canine experimental model has been developed to study the patterns of tissue ingrowth in allografts treated with different methods, providing insights into optimizing graft performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monocusp aortic valve replacement in dogs: an experimental model. Goldstein, J., Robinson, MC., McDonald, GR., et al.[2019]

Heart valve allografts, or homografts, have been used for over 45 years in cardiac surgery and are particularly important for valve replacement in congenital heart disease, with around 700 grafts provided annually by tissue banks in the UK and Eire.

The article reviews the performance of homografts compared to prosthetic alternatives, discussing their clinical applications, degeneration, and future developments in homograft technology, highlighting their ongoing relevance in surgical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What tissue bankers should know about the use of allograft heart valves. Barron, DJ., Khan, NE., Jones, TJ., et al.[2016]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Trends in pediatric donor heart discard rates and the potential use of unallocated hearts for allogeneic valve transplantation. [2023]

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

Candida albicans endocarditis associated with a contaminated aortic valve allograft--California, 1996. [2008]

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

The allograft valve in heart transplantation and valve replacement. Genetic assessment of the origin of the cells by means of deoxyribonucleic acid profiles. [2006]

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

Prevention of allograft heart valve failure in a rat model. [2013]

5. Italy pubmed.ncbi.nlm.nih.gov

Allograft replacement of the aortic valve for active endocarditis. [2016]

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

Partial Heart Transplantation in Adult Cardiac Surgery. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

T lymphocytes mediate leaflet destruction and allograft aortic valve failure in rats. [2019]

8. Australia pubmed.ncbi.nlm.nih.gov

Monocusp aortic valve replacement in dogs: an experimental model. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

What tissue bankers should know about the use of allograft heart valves. [2016]