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

Trial Summary

What is the purpose of this trial?

This will be a prospective, randomized study performed at a single tertiary referral academic medical center (University of California San Francisco, CA), evaluating the survival benefits of levothyroxine compared with no levothyroxine for patients who have undergone heart transplant. It will be double-blinded and placebo-control; participants will be randomized to receive levothyroxine or receive no levothyroxine.

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.

What data supports the effectiveness of the drug Levothyroxine for heart transplant recipients?

Levothyroxine is used in brain-dead organ donors to stabilize heart function and prevent heart failure, which suggests it might help heart transplant recipients by supporting heart health. ^{1 2 3 4 5}

Is levothyroxine generally safe for humans?

Levothyroxine is generally safe for humans, but there are rare cases of liver dysfunction, especially with rapid dose increases. It's important to start with smaller doses and increase slowly to avoid potential side effects. ^{2 3 6 7 8}

How is the drug Levothyroxine unique for heart transplant recipients?

Levothyroxine is unique for heart transplant recipients because it can help stabilize heart function and prevent cardiovascular collapse, which is crucial for maintaining the viability of the transplanted organ. This use is different from its typical role in treating thyroid hormone deficiencies. ^{1 2 3 4 6}

Research Team

Jason Smith, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

I am on the waiting list for a heart transplant.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 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]

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]

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]

References

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

The role of thyroid hormone administration in potential organ donors. [2019]

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

Stability of levothyroxine sodium 0.4 microg/mL in 0.9% sodium chloride injection. [2022]

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

Levothyroxine replacement therapy in patients with subclinical hypothyroidism and coronary artery disease. [2021]

4. England 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. [2016]

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

Intravenous Levothyroxine for Unstable Brain-Dead Heart Donors. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Levothyroxine Treatment of Euthyroid Children with Autoimmune Hashimoto Thyroiditis: Results of a Multicenter, Randomized, Controlled Trial. [2022]

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

New levothyroxine formulation meeting 95-105% specification over the whole shelf-life: results from two pharmacokinetic trials. [2018]

8. Japan 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. [2020]