Randomized Controlled Trial of Talc Instillation In Addition To Daily Drainage Through a Tunneled Pleural Catheter to Improve Rates of Outpatient Pleurodesis in Patients With Malignant Pleural Effusion

Randomized Controlled Trial of Talc Instillation In Addition To Daily Drainage Through a Tunneled Pleural Catheter to Improve Rates of Outpatient Pleurodesis in Patients With Malignant Pleural Effusion - The ASAP II Trial

The purpose of this study is to compare the experiences of subjects who drain malignant (cancerous) pleural effusions (fluid) from around their lung(s) in a more frequent manner using a talc instilled via tunneled pleural catheter combined with daily drainage and those subjects who drain this fluid in a daily standard manner.

Study Overview

• Status: Terminated
• Conditions: Malignant Pleural Effusion
• Intervention / Treatment: Drug: Talc

Detailed Description

Study Activities: Patients will be randomized to either the standard daily drainage group or the talc instilled via tunneled pleural catheter combined with standard daily drainage group. Patients will complete questionnaires regarding their health. If you are randomized to the talc group, you will receive talc infused through the tunneled pleural catheter. If you are randomized to the standard daily drainage group, you will not receive any additional therapy. Patients will complete a drainage diary for everyday they drain fluid which will provide information on drainage volume, fluid color, pain, and complications. At 30 days and 90 days post randomization, patients will return to clinic for follow-up, at which time they will have a physical exam, chest x-ray, and complete questionnaires regarding their health.

Risks/Safety Issues: Risks associated with talc include fever and pain. Less likely risks associated with talc include infection, dyspnea, hypoxemia, pneumonia, unilateral pulmonary edema, hemoptysis, pulmonary emboli, and bronchopleural fistula.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female, at least 18 years of age, inclusive.

2. Subject has a symptomatic MPE requiring intervention. For an effusion to be defined as malignant, at least one of the following must be true:

   1. There is histocytological confirmation of pleural malignancy
   2. The effusion is an exudate (per Light's criteria) in the context of histocytologically proven malignancy elsewhere, with no other clear cause for fluid identified.
3. Subject has a history of at least 1 ipsilateral pleural effusion causing dyspnea that responded to thoracentesis where the lung expanded and the dyspnea was improved.
4. Subject is willing and able to provide written informed consent.
5. Subject is willing and able to meet all study requirements, including follow-up visits and receiving study-related telephone calls.
6. Subject has sufficient pleural fluid to allow safe insertion of an IPC.
7. Subject has negative pregnancy test if appropriate.
8. Subject or caregiver is able to perform home drainage of the pleural effusion (a caregiver can be a friend, family member, or paid healthcare professional).

Exclusion Criteria:

1. Subject has significant trapped lung, or a proximal bronchial obstruction which is likely to lead to trapped lung. For a subject to be eligible for this study, two separate study center clinicians must agree that there is no significant trapped lung on the same CXR using visual estimation (reference guide). The CXR used to make this decision must have been performed ≤30 days preceding the consent form being signed, and must have been performed preferably on the same day, but no more than 7 calendar days after tunneled pleural catheter insertion. Significant trapped lung is deemed present if any 1 of the following criteria is met:

   1. A CXR shows hydropneumothorax other than small (< 1 cm between chest wall and pleural line) apical pneumothoraces.
   2. A CXR shows ≥20% of the affected hemithorax to be free of the expected lung parenchymal markings and there is no suggestion of pleural fluid.
   3. A CXR shows ≥20% of the affected hemithorax to be occupied with pleural fluid AFTER a pleural aspiration which resulted in symptoms suggestive of trapped lung (e.g., chest pain or cough).
2. Subject has a Karnofsky score <50, or a World Health Organization (WHO)/ Eastern Cooperative Oncology Group (ECOG) performance status ≥3. Subjects who have a performance status of 3 may be considered for the study if the removal of their fluid would likely improve their performance score by 1 or more.
3. Subject is pregnant, planning to become pregnant, or is lactating.
4. Subject has a history of empyema.
5. Subject has a history of chylothorax.
6. Subject has an uncorrected coagulopathy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Talc instilled via tunneled pleural catheter combined with standard daily drainage; This arm consists of eligible participants who are randomized to the Talc arm and would receive Talc therapy instilled into the pleural catheter.	Drug: Talc; All patients randomized to the Talc arm will receive Talc therapy through the pleural catheter.
No Intervention: Standard daily drainage; This arm consists of eligible participants who are randomized to control group and would not receive any intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Undergoing Accelerated Pleurodesis	Up to 90 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dyspnea as Measured by Questionnaire	Borg Dyspnea Scale was used to rate difficulty of breathing. This scale starts at number 0 where breathing is causing no difficulty at all and progresses through to number 10 where breathing difficulty is maximal. Lower scores on this scale equal a better outcome.	Baseline, 30 days, 90 Days
Qualify of Life as Measured by Short Form 36 Health Survey (SF-36) at Baseline	Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36) was evaluated for overall health status. The SF-36 is composed of eight multi-item scales (Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Energy/fatigue, Emotional well-being, Social functioning, Pain, General health), with scores for each of these scales (or dimensions) ranging from 0 to 100. Higher scores indicate higher qualify of life.	Baseline
Qualify of Life as Measured by Short Form 36 Health Survey (SF-36) at 30 Days	Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36) was evaluated for overall health status. The SF-36 is composed of eight multi-item scales (Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Energy/fatigue, Emotional well-being, Social functioning, Pain, General health), with scores for each of these scales (or dimensions) ranging from 0 to 100. Higher scores indicate higher qualify of life.	30 days
Qualify of Life as Measured by Short Form 36 Health Survey (SF-36) at 90 Days	Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36) was evaluated for overall health status. The SF-36 is composed of eight multi-item scales (Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Energy/fatigue, Emotional well-being, Social functioning, Pain, General health), with scores for each of these scales (or dimensions) ranging from 0 to 100. Higher scores indicate higher qualify of life.	90 days

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Scott Shofer, Duke University

Publications and helpful links

General Publications

• Wahidi MM, Reddy C, Yarmus L, Feller-Kopman D, Musani A, Shepherd RW, Lee H, Bechara R, Lamb C, Shofer S, Mahmood K, Michaud G, Puchalski J, Rafeq S, Cattaneo SM, Mullon J, Leh S, Mayse M, Thomas SM, Peterson B, Light RW. Randomized Trial of Pleural Fluid Drainage Frequency in Patients with Malignant Pleural Effusions. The ASAP Trial. Am J Respir Crit Care Med. 2017 Apr 15;195(8):1050-1057. doi: 10.1164/rccm.201607-1404OC.
• Bhatnagar R, Keenan EK, Morley AJ, Kahan BC, Stanton AE, Haris M, Harrison RN, Mustafa RA, Bishop LJ, Ahmed L, West A, Holme J, Evison M, Munavvar M, Sivasothy P, Herre J, Cooper D, Roberts M, Guhan A, Hooper C, Walters J, Saba TS, Chakrabarti B, Gunatilake S, Psallidas I, Walker SP, Bibby AC, Smith S, Stadon LJ, Zahan-Evans NJ, Lee YCG, Harvey JE, Rahman NM, Miller RF, Maskell NA. Outpatient Talc Administration by Indwelling Pleural Catheter for Malignant Effusion. N Engl J Med. 2018 Apr 5;378(14):1313-1322. doi: 10.1056/NEJMoa1716883.

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2021
• Primary Completion (Actual): October 7, 2022
• Study Completion (Actual): October 7, 2022

Study Registration Dates

• First Submitted: March 8, 2021
• First Submitted That Met QC Criteria: March 8, 2021
• First Posted (Actual): March 11, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Pleural Effusion, Malignant; Pleural Effusion
• Other Study ID Numbers: Pro00107258

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No