Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Compare the Efficacy and Safety of Intrapleural Doxycycline Versus Iodopovidone for Performing Pleurodesis in Malignant Pleural Effusion

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02583282
Recruitment Status : Recruiting
First Posted : October 22, 2015
Last Update Posted : September 3, 2018
Sponsor:
Information provided by (Responsible Party):
Ritesh Agarwal, Postgraduate Institute of Medical Education and Research

Brief Summary:
Malignant pleural effusion (MPE) arises in advanced-stages of malignancies and frequently heralds a poor prognosis.If the underlying malignancy is chemo sensitive (e.g., small-cell carcinoma of lung & lymphoma), systemic chemotherapy may control the pleural effusion. Instilling of sclerosing agents into the pleural cavity (pleurodesis) is a common method for the management of MPE. According to a recent survey, tetracycline or its derivative (doxycycline) is the preferred agent for performing pleurodesis at many centers. In a previous study from the investigators' center, the investigators have demonstrated equal efficacy of iodopovidone in comparison to talc in inducing pleural symphysis. Also, iodopovidone has been postulated to have anti-neoplastic effects and hence may help in reducing the drain output. Apart from these benefits iodopovidone is easily available and is cost effective. The investigators believe that iodopovidone will have better efficacy than doxycycline in inducing pleurodesis in malignant pleural effusion.

Condition or disease Intervention/treatment Phase
Malignant Pleural Effusion Other: Doxycycline Other: Iodopovidine Not Applicable

  Hide Detailed Description

Detailed Description:

Introduction & Review of literature Malignant pleural effusion (MPE) arises in advanced-stages of malignancies and frequently heralds a poor prognosis. Most patients with MPE are symptomatic. The most common symptom is exertional dyspnea. Most patients undergo chemotherapy or local treatments to palliate symptoms such as dyspnea, cough & chest pain, to improve quality of life. If the underlying malignancy is chemo sensitive (e.g., small-cell carcinoma of lung & lymphoma), systemic chemotherapy may control the pleural effusion.1 However, when pleural effusion persists or reaccumulates after chemotherapy, the management of refractory MPE includes local therapeutic methods such as thoracentesis, pleurodesis, pleurectomy, or pleuroperitoneal shunting. Instilling of sclerosing agents into the pleural cavity (pleurodesis) is a common method for the management of MPE. For several years, various agents such as anti-neoplastics (e.g., nitrogen mustard, bleomycin), tetracycline derivatives, talc, erythromycin, silver nitrate, and povidone-iodine have been injected into the pleural cavity to create pleurodesis.

According to a recent survey, tetracycline or its derivative (doxycycline) is the preferred agent for performing pleurodesis at many centers.7 However, intravenous preparation of doxycycline is not freely available and also induces severe inflammation in the pleura that results in severe chest pain and discomfort to the patient. In a previous study from the investigators' center, the investigators have demonstrated equal efficacy of iodopovidine in comparison to talc in inducing pleural symphysis.8 Also, iodopovidine has been postulated to have anti-neoplastic effects and hence may help in reducing the drain output. Apart from these benefits iodopovidine is easily available and is cost effective. The investigators believe that iodopovidone will have better efficacy than doxycycline in inducing pleurodesis in malignant pleural effusion.

Study hypothesis In patients with malignant pleural effusion, pleurodesis with intrapleural instillation of iodopovidone will have better efficacy in comparison with doxycycline.

Methods

Study design: This will be a randomized double blind study conducted in the Department of Pulmonary Medicine, PGIMER, Chandigarh.

Selection of cases: A total of 100 consecutive patients of malignant pleural effusion will be enrolled in the study. Patients will be equally randomized to undergo pleurodesis, either with intrapleural iodopovidone or intrapleural doxycycline. A written informed consent will be taken from all the patients participating in the present study

Randomization: Patient will be randomized 1:1 to undergo pleurodesis either by instillation of intrapleural iodopovidone or intrapleural doxycycline. The randomization sequence will be computer generated. The sequence generated will be kept in a sealed opaque envelope and will be opened at the time of procedure

Procedure: A chest tube (24-28 F) will be inserted through the fifth intercostal space in the mid-axillary line, to achieve complete drainage of the effusion and/or complete lung expansion. In case of large effusions, drainage will be spread over 24-48 h to prevent re-expansion pulmonary oedema. Pleurodesis will be performed when the daily drainage output will decrease to <150 mL/day and chest radiograph demonstrates apposition of pleural surfaces. In cases of pneumothorax, complete lung expansion and absence of any air leaks will be confirmed before instillation of the chemical agent. A chest radiograph will be performed to confirm complete re-expansion. Normal saline solution (50 mL) containing lignocaine (2 mg/kg ideal body weight) will be infused through the chest tube. Simultaneously, tramadol (100 mg) will be administered intravenously for analgesia. After 15 minutes pleurodesis will be performed either by instillation of doxycycline or by iodopovidone.

Doxycycline: 500 mg of doxycycline will be dissolved in 50 ml of normal saline. The combination will then be instilled through the chest tube in the pleural cavity and the chest tube drain will be clamped for 4 hours.

Iodopovidone: 20 ml of 10% betadine (Microshield, Johnson and Johnson, Solan, India) will be dissolved in 80 mL of normal saline. The combination will then be instilled through the chest tube in the pleural cavity and the chest tube drain will be clamped for 4 hours.

The chest tube will be flushed with 50 mL of normal saline after instillation of study drug (doxycycline or iodopovidone).

Endpoint: The chest tube will be removed if the drainage output is less than 100mL of pleural fluid and there is complete lung re-expansion with no residual pneumothorax on chest radiograph. Pulse, blood pressure, respiratory rate and temperature will be measured before and every 30 minutes after the procedure for 6 hours. Chest pain after pleurodesis will be recorded on a visual analogue scale (VAS) of 0-100 mm. Patients will be given additional intravenous tramadol (50 mg) on an as-needed basis after the procedure. Any complications related to the procedure will be recorded. Complications such as hypotension, fever, acute respiratory failure and empyema will be noted. Patients will be followed up at 1 week, at 1, 3 and 6 months.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A Study to Compare the Efficacy and Safety of Intrapleural Doxycycline Versus Iodopovidone for Performing Pleurodesis in Malignant Pleural Effusion
Actual Study Start Date : August 1, 2015
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Doxycycline
Intrapleural doxycycline
Other: Doxycycline
500 mg of doxycycline will be dissolved in 50 ml of normal saline. The combination will then be instilled through the chest tube in the pleural cavity and the chest tube drain will be clamped for 4 hours.

Active Comparator: Iodopovidine
Intrapleural iodopovidine
Other: Iodopovidine
20 ml of 10% betadine (Microshield, Johnson and Johnson, Solan, India) will be dissolved in 80 mL of normal saline. The combination will then be instilled through the chest tube in the pleural cavity and the chest tube drain will be clamped for 4 hours.




Primary Outcome Measures :
  1. Complete success [ Time Frame: 30 days ]
    long-term relief of symptoms related to the effusion, with absence of re-accumulation of fluid on chest radiograph at 30 days

  2. Partial success [ Time Frame: 30 days ]
    diminution of dyspnea related to the effusion, with only partial reaccumulation of fluid and no requirement for therapeutic thoracentesis

  3. Failed pleurodesis [ Time Frame: 30 days ]
    reaccumulation of pleural fluid requiring therapeutic thoracentesis, persistence of drainage output >250mL/day requiring repeat procedure, lack of success requiring surgical intervention


Secondary Outcome Measures :
  1. Time to pleurodesis [ Time Frame: 1 week ]
    interval between instillation of the agent and removal of the chest tube



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • recurrent symptomatic malignant pleural effusion, with subjective improvement of dyspnea following thoracentesis

Exclusion Criteria:

  • history of any allergy to iodine or doxycycline
  • history of thyroid disorders
  • failure of lung expansion after insertion of intercostal tube (trapped lung)
  • presence of air leaks
  • advanced malignancy with limited predicted life expectancy (<30 days)
  • failure to provide informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02583282


Locations
Layout table for location information
India
Bronchoscopy suite, PGIMER Recruiting
Chandigarh, India, 160012
Contact: Ritesh Agarwal, MD, DM    0172-2756825    riteshpgi@gmail.com   
Contact: Inderpaul S Sehgal, MD, DM    0172-2748215    ipdoc_2000@hotmail.com   
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research

Layout table for additonal information
Responsible Party: Ritesh Agarwal, Additional Professor, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT02583282     History of Changes
Other Study ID Numbers: INT/IEC/2015/232
First Posted: October 22, 2015    Key Record Dates
Last Update Posted: September 3, 2018
Last Verified: August 2018
Additional relevant MeSH terms:
Layout table for MeSH terms
Pleural Diseases
Anti-Bacterial Agents
Pleural Effusion, Malignant
Pleural Effusion
Respiratory Tract Diseases
Pleural Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Doxycycline
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents