Inhaled Tranexamic Acid for Bleeding in Cancer Patients

Overseen By Nisha Rathi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti-epileptics, Anti-fibrinolytics

Disqualifiers: DNR, 100% FIO2, COVID-19, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3-5 days

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if inhaled tranexamic acid, a medication used to reduce bleeding, can improve survival rates in cancer patients with severe lung bleeding and breathing difficulties. It compares the effects of this treatment with usual care. Participants will be divided into two groups: one receiving inhaled tranexamic acid and the other receiving standard care. The trial seeks individuals with blood cancer who are on a breathing machine and have persistent bloody secretions from their lungs. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on anti-fibrinolytic therapy (medications that prevent blood clots from breaking down).

Is there any evidence suggesting that inhaled tranexamic acid is likely to be safe for humans?

Research has shown that inhaled tranexamic acid (TXA) is generally safe for treating bleeding in the lungs. In studies with cancer patients, TXA did not lead to more serious bleeding or blood clots. The common side effects resembled those of other treatments. Additionally, findings suggest that using TXA in mist form (nebulized) controls bleeding as effectively as other standard treatments. This evidence supports its safety for managing lung bleeding in cancer patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for bleeding in cancer patients, which often involve systemic administration of tranexamic acid, this approach uses an inhaled form. This is unique because inhaling the medication allows it to be delivered directly to the lungs, where bleeding often occurs in cancer patients, potentially offering faster and more targeted relief. Researchers are excited because this method could reduce side effects associated with systemic administration and improve patients' quality of life by addressing bleeding more efficiently and comfortably.

What evidence suggests that inhaled tranexamic acid might be an effective treatment for cancer-related pulmonary hemorrhage?

Research has shown that inhaled tranexamic acid, which participants in this trial may receive, effectively controls bleeding in the lungs. In one study, 95% of patients stopped bleeding completely within 48 hours of use. Another case demonstrated its effectiveness in stopping severe bleeding in a patient with a cancerous tumor in the airway. Reports also indicate significant symptom improvement in patients who frequently experience lung bleeding after using this treatment. These findings suggest that inhaled tranexamic acid could help manage bleeding in cancer patients. Meanwhile, other participants in this trial will receive usual care, serving as a comparison to evaluate the effectiveness of inhaled tranexamic acid. ^{1 2 3 4 5}

Who Is on the Research Team?

Nisha Rathi, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with blood cancers who are on mechanical ventilation due to lung bleeding. They must be expected to live more than 48 hours, not have a severe brain bleed, no DNR orders, and not be pregnant or have COVID-19. People with recent blood clots, known allergies to tranexamic acid, color vision issues, seizures under treatment, or prior use of inhaled tranexamic acid can't join.

Inclusion Criteria

Evidence of diffuse alveolar hemorrhage by bronchoscopic examination

Persistently bloody secretions upon endotracheal tube suctioning

I have signed the consent form, or my legal representative has.

Exclusion Criteria

You have a nose or mouth that is bleeding and causing bloody secretions.

I am currently taking medication for epilepsy.

I am currently infected with COVID-19.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive inhaled tranexamic acid or usual care for pulmonary hemorrhage

3-5 days

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

Extended Follow-up

Monitoring of secondary outcomes such as ICU and hospital mortality rate, ventilator days, and length of stay

100 days

What Are the Treatments Tested in This Trial?

Interventions

• Tranexamic Acid
• Usual Care

Trial Overview The study tests if breathing in the drug tranexamic acid helps reduce death rates in cancer patients with lung bleeding compared to standard treatments. Patients will either receive the usual care or the added inhalation therapy and their survival outcomes will be compared.

How Is the Trial Designed?

Group I: Group B: Usual Care Experimental Treatment 1 Intervention

usual care

Group II: Group A: Inhaled tranexamic acid Experimental Treatment 1 Intervention

will receive 500 mg/5ml nebulized tranexamic acid every 8 hours for at least 3 days, and up to 5 days

Tranexamic Acid is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Approved in European Union as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries
• Hereditary angioedema

Approved in Canada as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Approved in Japan as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

A systematic review of 57 studies involving 5,049 patients found that the antifibrinolytic drug tranexamic acid (TXA) has a low frequency of thrombotic events, with less than 1% incidence of limb ischaemia and myocardial infarction.

For patients treated with TXA or epsilonaminocaproic acid (EACA) after spontaneous bleeding, the occurrence of deep vein thrombosis or pulmonary embolism was 1.9% and 3.0%, respectively, indicating that these drugs are generally safe, especially outside of subarachnoid haemorrhage cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The frequency of thrombotic events among adults given antifibrinolytic drugs for spontaneous bleeding: systematic review and meta-analysis of observational studies and randomized trials. Ross, J., Al-Shahi Salman, R.[2022]

In a study of 83 patients undergoing spinal tumor surgery, the use of tranexamic acid (TXA) did not significantly reduce overall, intraoperative, or postoperative blood loss, indicating its moderate efficacy in this context.

However, the TXA group experienced a significant reduction in the volume of blood transfusions needed, without any increase in postoperative complications, suggesting that TXA may help minimize the need for transfusions during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood loss and perioperative transfusions related to surgery for spinal tumors. Relevance of tranexamic acid. Damade, C., Tesson, G., Gilard, V., et al.[2020]

A case study demonstrated that nebulized tranexamic acid (TXA) effectively resolved significant hemoptysis in a patient with an invasive airway malignancy within 15 minutes, indicating its rapid action.

The use of nebulized TXA appears to be a safe and noninvasive option for managing hemoptysis, suggesting its potential as a palliative treatment for patients experiencing chronic or acute bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nebulized Tranexamic Acid as a Noninvasive Therapy for Cancer-Related Hemoptysis. Hankerson, MJ., Raffetto, B., Mallon, WK., et al.[2015]

In a study of 282 cancer patients undergoing hip or knee arthroplasty, the use of tranexamic acid (TXA) did not increase the risk of complications such as venous thromboembolism within 90 days or 1 year, suggesting it is safe for this population.

TXA was associated with a trend towards lower risk of complications, indicating that it may be beneficial for reducing blood loss in cancer patients undergoing surgery without compromising their safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid in patients with current or former cancer undergoing hip and knee arthroplasty. Varady, NH., Chen, AF., Drayer, NJ., et al.[2021]

Inhaled tranexamic acid (TXA) is effective in quickly controlling bleeding in patients with non-massive haemoptysis, based on the best available evidence from a review of 34 papers.

The review highlights that nebulized TXA leads to a fast resolution of bleeding, suggesting it could be a beneficial treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BET 1: Does inhaled tranexamic acid reduce morbidity in adults with haemoptysis? Mervau, J., Jason, S., Jones, JS.[2020]

In a review of five studies involving 20,047 patients, tranexamic acid (TXA) significantly reduced short-term mortality in patients with hemoptysis, with a risk ratio of 0.78, indicating a 22% lower risk of death compared to controls.

TXA also led to shorter bleeding times and hospital stays, and reduced the need for further medical interventions, all without increasing the risk of major or minor adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does tranexamic acid reduce risk of mortality on patients with hemoptysis?: A protocol for systematic review and meta-analysis. Chen, LF., Wang, TC., Lin, TY., et al.[2023]

Locally injected tranexamic acid (TXA) at a concentration of 1 mg/mL significantly improved the clarity of the surgical field during subcutaneous tumor excisions, especially in patients on antithrombotic drugs, leading to better surgical outcomes.

The use of TXA also reduced the incidence of minor postoperative complications, such as hematomas and infections, and shortened hospital stays by allowing for quicker drain removal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of local infiltration of tranexamic acid in subcutaneous surgery: A protocol from a single medical center. Chang, YJ., Lin, YH., Wang, PL., et al.[2023]

In a study of 164 patients undergoing total hip replacement, a single injection of 30 mg/kg tranexamic acid (TXA) was found to be as effective as a continuous infusion in reducing blood loss, with no significant difference in mean blood loss between the two methods.

Both treatment methods were safe, with no reported deaths or major thromboembolic events within 90 days post-surgery, suggesting that the single injection is a practical and effective option for routine use in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single tranexamic acid dose to reduce perioperative morbidity in primary total hip replacement: a randomised clinical trial. Hourlier, H., Fennema, P.[2023]

In a clinical trial involving 356 patients with hematologic malignancies, prophylactic use of tranexamic acid (TXA) did not significantly reduce the incidence of WHO grade ≥2 bleeding compared to a placebo, with bleeding observed in 50.3% of the TXA group and 54.2% of the placebo group.

There were no significant differences in platelet transfusions, days alive without bleeding, or serious adverse events between the TXA and placebo groups, indicating that TXA may not be effective for preventing bleeding in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic tranexamic acid in patients with hematologic malignancy: a placebo-controlled, randomized clinical trial. Gernsheimer, TB., Brown, SP., Triulzi, DJ., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11717782/

Advances in the study of nebulized tranexamic acid for ... In terms of efficacy, inhaled TXA was effective in 18 patients (95%), achieving resolution of pulmonary hemorrhage within 48 h of administration ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05053867

A Randomized Controlled Trial of Inhaled Tranexamic Acid ... This is a drug study that will examine if inhaled tranexamic acid can improve mortality in patients with cancer-related pulmonary hemorrhage and respiratory ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0300289625002285

Nebulized Tranexamic Acid in Low- to Medium-abundance ... Nebulized tranexamic acid (NebTXA) appeared effective for mild to moderate bleeding, particularly in single-episode cases without oxygen ...

4. withpower.com withpower.com/trial/early-phase-1-hemorrhage-2022-18b34

Inhaled Tranexamic Acid for Bleeding in Cancer Patients A case study demonstrated that nebulized tranexamic acid (TXA) effectively resolved significant hemoptysis in a patient with an invasive airway malignancy ...

5. intjem.biomedcentral.com intjem.biomedcentral.com/articles/10.1186/s12245-020-00304-x

Nebulized tranexamic acid for recurring hemoptysis in ... Our paper demonstrates three cases where patients presented with significant hemoptysis and had significant improvement in symptoms following ...