TXA Nebulization for the Treatment of Hemoptysis

Study Overview
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Brief Summary
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Hemoptysis is a common presentation in medical emergency. Prompt medical therapy, bronchoscopic and endovascular procedures remains the cornerstone of management for both diagnostic as well as therapeutic purpose in hemoptysis. Priority is given for medical management to achieve hemostasis and prevent aspiration as well as treatment of underlying etiology, before undertaking any definitive bronchoscopic or endovascular intervention. While majority of the patients are managed successfully by prompt medical therapy, only the refractory cases and life-threatening hemoptysis need more definitive procedures like DSA guided bronchial artery embolization and bronchoscopic procedures like endobronchial biocompatible glue, endobronchial embolization using silicone spigots, endobronchial stents, laser photocoagulation. Tranexamic acid is an anti-fibrinolytic agent which prevent breakdown of fibrin clots, thus helping in clot stabilization and controlling bleeding. As a medical therapy Tranexamic Acid is used for bleeding control in hemoptysis as well as other surgical or traumatic bleeding. Previously conducted institutional study comparing IV infusion of TXA to placebo in patients with sub massive hemoptysis showed results favoring TXA over placebo in terms of decreasing frequency & quantity of hemoptysis, duration of hospital stay and need for DSA/ broncoscopic/ surgical intervention and blood transfusion (1). While the oral and IV routes have been most commonly studied, use of novel approaches like aerosolized TXA and endobronchial instillation of TXA during bronchoscopy have showed positive results in achieving hemostasis in hemoptysis (2). A recently conducted RCT, to assess the effectiveness of TXA nebulization in sub-massive hemoptysis concluded that nebulized TXA is effective in reducing the frequency and quantity of hemoptysis. Nebulized TXA was also found to be safe as no severe ADR was noted during its use as per previous RCT as well as multiple case reports. However, because of limited number of research with small sample size and barring some case reports evidence for the use of nebulized TXA is limited in hemoptysis. In hemoptysis nebulized form of TXA is supposed to reach local site of bleeding (lung/ airway) promptly at a higher concentration leading to rapid control of hemoptysis. So, this study has been planned to evaluate further this novel approach of TXA nebulization for the management of hemoptysis. Similarly, data regarding adverse drug reaction related to TXA nebulization is also limited. This study will produce additional information regarding efficacy, safety and ADR related to TXA nebulization.

Official Title
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Efficacy of TXA Nebulization for the Treatment of Hemoptysis: A Randomized Controlled Clinical Trial

Conditions
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Hemoptysis

Intervention / Treatment
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* Drug: TXA Nebulization
* Other: 0.9% NS Nebulization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All cases of active hemoptysis irrespective of gender age≥ 18 years Exclusion Criteria: Massive hemoptysis Pregnancy Drug allergy to TXA4 Renal failure Receiving Oral Contraceptive Pills. Already on blood thinner Not willing for consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: TXA<br>Nebulization with TXA 500mg/ 5mL 8 hourly for 2 days. | Drug: TXA Nebulization<br>* Nebulization with TXA 500mg/ 5mL 8 hourly for 2 days plus standard care of therapy<br>|
| Placebo Comparator: Control<br>Nebulization with 0.9%normal saline 5mL 8 hourly for 2 days | Other: 0.9% NS Nebulization<br>* Nebulization with 0.9% normal saline (NS) 5mL 8 hourly for 2 days plus standard care of therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of hemoptysis | Number of episode of hemoptysis per day will be compared at baseline and day 2 (48 hours) | 48 hours | 
| Quantity of hemoptysis | Through collection of expectorated blood, quantityofhemoptysis per day will be compared at baseline and day2 (48hours) . | 48 hours | 
| Visual analogue scale (VAS) | Visual subjective assessment by the patient will be used to compare the amount of hemoptysis at baseline and day 2 (48 hours). VAS will be presented to the patients as a 100 mm line anchored by description with 'no-hemoptysis' at one end and 'worst imaginable hemoptysis' on the other end. Patients will be asked to mark a point on the 100 mm line to indicate the severity. A millimeter scale will be used to measure the score and this will provide 0-100 levels of hemoptysis and the score increases with increasing severity. | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse drug events | Frequency/number of adverse drug events will be compared between the groups. | 48 hours | 
| Resolution of hemoptysis | Resolution of hemoptysis is defined as no episode of hemoptysis containing fresh blood sustained for at least 48 hours following cessation of hemoptysis. The rate of resolution of hemoptysis will be compared between the groups. | 48 Hours | 
| Need for intervention | The overall the rate of the need for therapeutic interventional procedures (BAE, bronchoscopic procedures), to achieve hemostasis, will be compared between the study and control group. | 48 Hours | 
| Need for blood transfusion | The percentage of patients requiring blood transfusion as well as the mean number of PRBCs transfused will be compared between the groups. | 48 Hours | 
| Duration of hospital stay | The total duration of hospital stay (from the day of admission to the day of discharge or death) will be compared between both the groups. | 4 weeks | 
| Mortality | All patients will be followed up at day 28, physically or telephonically to assess the mortality as well as their well-being. The rate of mortality will be compared between the groups. | 4 weeks | 
| Recurrence of hemoptysis | Recurrence will be defined as fresh episode of hemoptysis after resolution during 28 days follow-up. The rate of recurrence of hemoptysis will be compared between the groups. | 4 weeks |