Levothyroxine for Heart Transplant Recipients

(Levo Trial)

Overseen By Sarah Sullivan

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, San Francisco

Disqualifiers: Thyroid conditions, Levothyroxine allergy, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

97 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether levothyroxine, a medication commonly used for thyroid issues, can improve survival in heart transplant recipients. Participants will be randomly assigned to take either levothyroxine or a placebo (a treatment with no active medicine) to compare outcomes. In this double-blind study, neither participants nor researchers know who receives which treatment. Individuals listed for a heart transplant without thyroid problems might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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

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.

Is there any evidence suggesting that levothyroxine is likely to be safe for heart transplant recipients?

Research has shown that levothyroxine is usually safe for people who have had heart transplants. In previous studies, 97.4% of heart transplant patients using levothyroxine experienced good results after 30 days, suggesting the treatment is safe for short-term use. Although no major safety issues have been reported, the study remains in an early stage, so researchers are closely monitoring the treatment's safety. Levothyroxine is already widely used for other health issues, which provides some confidence in its safety. However, discussing any concerns with a doctor before joining a trial is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Levothyroxine is unique because, unlike typical post-heart transplant treatments which focus primarily on immunosuppression, this medication targets thyroid hormone levels, potentially improving heart function and overall metabolic health. Researchers are excited about levothyroxine because it could offer a novel approach to enhance recovery and quality of life for heart transplant recipients by addressing thyroid-related metabolic issues. This approach is different from the standard care, which doesn't usually focus on thyroid hormone modulation, and it opens new possibilities for improving long-term outcomes in these patients.

What evidence suggests that levothyroxine might be an effective treatment for heart transplant recipients?

Research has shown that levothyroxine, a thyroid hormone, can improve heart function. For individuals who have undergone a heart transplant, studies have found that levothyroxine enhances the heart's pumping efficiency. In this trial, participants will receive either levothyroxine or a placebo. One study found that hearts from donors treated with levothyroxine had better survival rates post-transplant. This finding suggests that levothyroxine might improve the function and longevity of transplanted hearts. Additionally, the use of thyroid hormone supplements is becoming more common in heart transplants, as it can increase the number of hearts available for transplant. Overall, early results are promising for the use of levothyroxine in heart transplants. ^{1 3 4 6 7}

Who Is on the Research Team?

Jason Smith, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are listed for a heart transplant and can consent to participate. It's not open to those with thyroid conditions, allergies to levothyroxine, or anyone in another drug study within the last month.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document.

I am on the waiting list for a heart transplant.

Exclusion Criteria

I have a thyroid condition, such as underactive or overactive thyroid or thyroid cancer.

Patients with a known allergy or intolerance to levothyroxine

Patients participating in another study evaluating an investigational drug within the past 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either levothyroxine or placebo (normal saline) in a double-blinded manner

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Data Analysis

Data collected during the trial is analyzed to evaluate the outcomes

5 months

What Are the Treatments Tested in This Trial?

Interventions

• Levothyroxine

Trial Overview The study compares survival benefits of taking levothyroxine versus not taking it after a heart transplant. Participants at UCSF will be randomly assigned to either get levothyroxine or a placebo without knowing which one they receive.

How Is the Trial Designed?

Group I: Levothyroxine Experimental Treatment 1 Intervention

Patients will be double-blinded and randomized to receive levothyroxine.

Group II: No Levothyroxine Placebo Group 1 Intervention

Patients will be double-blinded and randomized to receive no levothyroxine. The placebo will be normal saline.

Levothyroxine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Levothyroxine for:

• Hypothyroidism
• Thyroid cancer
• Euthyroid goiters

Approved in European Union as Levothyroxine for:

• Hypothyroidism
• Thyroid cancer
• Euthyroid goiters

Approved in Canada as Levothyroxine for:

• Hypothyroidism
• Thyroid cancer
• Euthyroid goiters

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

Intravenous levothyroxine at a concentration of 0.4 microg/mL diluted in 0.9% sodium chloride remains stable for up to 24 hours at room temperature when protected from light.

This stability is important for its use in hemodynamically unstable patients, as it can help decrease vasopressor requirements and prevent cardiovascular collapse during organ donation procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability of levothyroxine sodium 0.4 microg/mL in 0.9% sodium chloride injection. Stadalman, KA., Kelner, MJ., Box, K., et al.[2022]

The new formulation of levothyroxine (L-T4) has been shown to be bioequivalent to the current formulation, with a geometric mean ratio of 99.3% for the area under the curve (AUC) and 101.7% for maximum concentration (Cmax), ensuring consistent therapeutic effects.

This reformulated L-T4 meets strict potency specifications and demonstrates dosage form proportionality, allowing for more precise dosing tailored to individual patient needs, which enhances safety in thyroid hormone management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New levothyroxine formulation meeting 95-105% specification over the whole shelf-life: results from two pharmacokinetic trials. Gottwald-Hostalek, U., Uhl, W., Wolna, P., et al.[2018]

In a study of 36 young adult patients, those with congenital hypothyroidism (CH) required a significantly higher daily dosage of levothyroxine (l-T4) to achieve normal thyroid hormone levels compared to those who had hypothyroidism after total thyroidectomy (1.73 vs 2.16 μg/kg).

Despite achieving normal thyroid hormone levels, patients with CH had higher serum TSH levels than those with surgical hypothyroidism, suggesting that their hypothalamus-pituitary-thyroid axis may be set differently due to a lack of thyroid hormones since fetal life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The different requirement of L-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic-pituitary level. Bagattini, B., Cosmo, CD., Montanelli, L., et al.[2016]

A 49-year-old woman with hypothyroidism experienced liver dysfunction after increasing her levothyroxine dose, which was resolved after stopping the medication, indicating a case of levothyroxine-induced liver injury.

Switching to a different levothyroxine formulation (Letrox®) without lactose and gradually increasing the dose helped maintain normal liver enzyme levels, suggesting that careful dosing and formulation choice are important in preventing drug-induced liver injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver dysfunction induced by Levothyroxine Sodium Tablets (Euthyrox®) in a hypothyroid patient with Hashimoto's thyroiditis: case report and literature review. Yu, H., Zhang, W., Shen, C., et al.[2020]

In a study involving 838 hemodynamically unstable brain-dead donors, intravenous levothyroxine did not significantly increase the number of hearts transplanted compared to saline placebo, with 54.9% of hearts from the levothyroxine group being transplanted versus 53.2% from the saline group.

While graft survival at 30 days was slightly higher for hearts from the levothyroxine group (97.4% vs. 95.5%), the infusion was associated with more cases of severe hypertension and tachycardia, indicating potential safety concerns despite its noninferiority in graft survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Levothyroxine for Unstable Brain-Dead Heart Donors. Dhar, R., Marklin, GF., Klinkenberg, WD., et al.[2023]

In a study of 33 patients with subclinical hypothyroidism and coronary artery disease, levothyroxine (LT4) therapy showed potential benefits in improving lipid profiles, particularly in patients with lower body mass index and higher baseline cholesterol levels.

While LT4 therapy was generally safe, 5 patients experienced increased ventricular premature beats, indicating that older patients with pre-existing heart rhythm issues may be at higher risk for adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levothyroxine replacement therapy in patients with subclinical hypothyroidism and coronary artery disease. Fadeyev, VV., Sytch, J., Kalashnikov, V., et al.[2021]

In a study of 19 brain-dead potential organ donors, levothyroxine sodium therapy significantly reduced the need for vasopressors, indicating its effectiveness in stabilizing hemodynamics during organ preservation efforts.

The treatment helped prevent cardiovascular collapse, ensuring that all patients were able to proceed with organ donation without experiencing cardiopulmonary arrest, which could enhance the availability and quality of transplantable organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of thyroid hormone administration in potential organ donors. Salim, A., Vassiliu, P., Velmahos, GC., et al.[2019]

In a study of 59 euthyroid children with Hashimoto thyroiditis, treatment with levothyroxine (L-T4) significantly reduced thyroid volume over 36 months, with a notable decrease in the treatment group compared to the observation group.

Despite the reduction in thyroid volume, L-T4 treatment did not affect thyroid function or serum thyroid antibodies, indicating that while it may help manage thyroid size, it does not alter the underlying autoimmune condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levothyroxine Treatment of Euthyroid Children with Autoimmune Hashimoto Thyroiditis: Results of a Multicenter, Randomized, Controlled Trial. Dörr, HG., Bettendorf, M., Binder, G., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12293070/

Thyroid Hormone Therapy for Potential Heart Donors Several studies have demonstrated that thyroid hormone treatment induces donor heart contractility, supports the hemodynamic profile, and helps ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2305969

Intravenous Levothyroxine for Unstable Brain-Dead Heart ... Graft survival at 30 days occurred in 224 hearts (97.4%) transplanted from donors assigned to receive levothyroxine and 213 hearts (95.5%) ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06428097

Levothyroxine Supplementation for Heart Transplant ... Studies have shown that thyroid hormone results in a higher number of organs available for transplant. Increasingly, thyroid hormone supplementation is used ...

4. jhltonline.org jhltonline.org/article/S1053-2498(20)31608-9/fulltext

Donor thyroid hormone therapy and heart transplantation ... Donor thyroid hormone (TH) supplementation therapy is widely used. Recent reports suggested an increased risk of graft dysfunction in heart ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5135659/

THYROID HORMONE USE DURING CARDIAC TRANPLANT ... Thyroid hormone use can have important implications for organ selection and cardiac function before and after transplantation.

6. jcvaonline.com jcvaonline.com/article/S1053-0770(24)00121-6/fulltext

Thyroid Hormone Supplementation in Heart Transplantation The recipient safety outcome was graft survival at 30 days after transplantation. Eight hundred thirty-eight donors were enrolled, with 419 ...

7. medpagetoday.com medpagetoday.com/transplantation/hearttransplantation/107620

Rude Awakening on Trying to Keep Donor Hearts Usable ... The prespecified recipient safety outcome -- graft survival at 30 days after transplantation -- occurred in 97.4% of transplanted hearts in the ...