A Study to Compare the Efficacy and Safety of Intrapleural Doxycycline Versus Iodopovidone for Performing Pleurodesis in Malignant Pleural Effusion
Condition: Malignant Pleural Effusion
MeSH terms: Pleural Effusion, Malignant; Pleural Effusion
Study type: Interventional

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.
    

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.
    

Intervention name(s): Doxycycline; Iodopovidine
Intervention type(s): Other; Other
Intervention description(s): 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.; 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.
Intervention MeSH terms: Doxycycline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care