Ibuprofen or Morphine in Treating Pain in Patients Undergoing Pleurodesis for Malignant Pleural Effusion

Study Overview
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Brief Summary
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RATIONALE: Morphine and ibuprofen help lessen pain caused by pleurodesis. It is not yet known whether one drug is more effective than the other in lessening pleurodesis-related pain or whether the size of the chest drain tube affects pain. PURPOSE: This randomized clinical trial is studying ibuprofen to see how well it works compared with morphine in treating pain in patients undergoing pleurodesis for malignant pleural effusion.

Detailed Description
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OBJECTIVES: Primary To evaluate the efficacy of a non-steroidal based regimen comprising ibuprofen in decreasing post-pleurodesis pain as compared to an opiate-based regimen comprising morphine sulfate in patients with malignant pleural effusion. To evaluate whether chest drain size influences the amount of post-pleurodesis pain. OUTLINE: This is a multicenter study. Patients are stratified according to histological tissue type (mesothelioma vs non-mesothelioma) and thoracoscopic procedure. Patients are randomized to 1 of 4 treatment arms. Arm I: Patients undergo pleurodesis after placement of a large bore chest drain (24F) on day 0 and receive oral ibuprofen 3 times daily for 3 days. The chest tube is removed on day 3. Arm II: Patients undergo pleurodesis after placement of a small bore chest drain (12F) on day 0 and receive oral ibuprofen 3 times daily for 3 days. The chest tube is removed on day 3. Arm III: Patients undergo pleurodesis after placement of a large bore chest drain (24F) on day 0 and receive oral morphine sulfate 4 times daily for 3 days. The chest tube is removed on day 3. Arm IV: Patients undergo pleurodesis after placement of a small bore chest drain (12F) on day 0 and receive oral morphine sulfate 4 times daily for 3 days. The chest tube is removed on day 3. All patients will receive regular background analgesia comprising paracetamol 4 times daily on days 0-3. Patients not adequately treated with these regimens may also receive rescue analgesia comprising morphine sulfate IV on days 0-3. After completion of study treatment, patients are followed at 1, 3, and 6 months, and periodically thereafter.

Official Title
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A 2 x 2 Factorial Trial to Assess Whether Non-Steroidal Anti-Inflammatory Analgesics and Small Bore Chest Tubes Are Less Painful Than Opiate Analgesics and a Large Bore Chest Tubes in Pleurodesis for Malignant Pleural Effusion [TIME1]

Conditions
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Metastatic Cancer

Intervention / Treatment
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* Drug: ibuprofen
* Drug: morphine sulfate
* Procedure: management of therapy complications
* Procedure: pleurodesis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of malignant pleural effusion requiring pleurodesis confirmed by 1 of the following: Histologically proven pleural malignancy Typical features of pleural malignancy seen on direct vision during thoracoscopy Pleural effusion in the context of histologically proven cancer elsewhere No primary lymphoma or small cell lung carcinoma All patients undergoing thoracoscopy for suspected malignant pleural effusion are eligible PATIENT CHARACTERISTICS: Life expectancy > 1 month Not pregnant or nursing No history of GI bleeding or untreated peptic ulceration No known sensitivity to non-steroidal anti-inflammatory drugs (NSAIDs), opiates, or paracetamol No hypercapnic respiratory failure No known intravenous drug abuse No severe renal or liver disease No known bleeding diathesis Able to give informed consent PRIOR CONCURRENT THERAPY: More than 2 weeks since prior and no concurrent corticosteroid therapy No concurrent warfarin therapy No other concurrent analgesics Analgesics used as a breakthrough regimen are allowed from trial entry to tube withdrawal at day 3 post-pleurodesis (i.e., regular paracetamol, assigned study analgesia, and breakthrough medication only, including opiate slow release patches) No concurrent enrollment on another clinical study Patients may participate in other trials immediately after completion of current trial, excluding those involving further pleural procedures or analgesia trials in which patients must wait at least 3 months after completion of current trial

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: Supportive Care
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ibuprofen|nan|
|Drug: morphine sulfate|nan|
|Procedure: management of therapy complications|nan|
|Procedure: pleurodesis|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average pain score over 72 hours post pleurodesis (total pain relief score) by a Visual Analogue Scale of pain relief and pain intensity every 6 hours |  |  | 
| Pleurodesis success at 3 months post randomization (time to relapse of pleural effusion, censored for survival) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of chronic chest pain on the side of the pleurodesis at 6 weeks and 3 months post randomization |  |  | 
| Change in hemoglobin and white cell count from day 0 to day 3 |  |  | 
| Change in renal function and liver function (i.e., ALT or AST, bilirubin, albumin, and alk phos) from day 0 to day 3 |  |  | 
| Change in Inflammatory markers from day 0 and day 3 (e.g., CRP, WCC) from day 0 to day 3 |  |  | 
| Change in alveolar PO2-arterial PO2 (A-a) gradient (on air) on day 0 and day 3 |  |  | 
| Continuous oximetry monitoring from day 0 to day 3 (on air unless saturation < 90%) |  |  | 
| Average conscious level measured by Glasgow Coma scale from day 0 to day 3 |  |  | 
| Drug- and talc-related adverse reactions |  |  | 
| Complications from chest drain insertion |  |  | 
| Presence of chronic chest wall pain assessed at all follow-up visits |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malignant pleural effusion