Official Title: “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]”

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.

Study Type: Interventional

Study Design: Supportive Care, Randomized

Study Primary Completion Date: September 2009

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.

Intervention(s) in this Clinical Trial

• Drug: ibuprofen
• Drug: morphine sulfate
• Procedure: management of therapy complications
• Procedure: pleurodesis

Primary Measures

• 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
  • Safety Issue?: No
• Pleurodesis success at 3 months post randomization (time to relapse of pleural effusion, censored for survival)
  • Safety Issue?: No

Secondary Measures

• Presence of chronic chest pain on the side of the pleurodesis at 6 weeks and 3 months post randomization
  • Safety Issue?: No
• Change in hemoglobin and white cell count from day 0 to day 3
  • Safety Issue?: Yes
• Change in renal function and liver function (i.e., ALT or AST, bilirubin, albumin, and alk phos) from day 0 to day 3
  • Safety Issue?: Yes
• Change in Inflammatory markers from day 0 and day 3 (e.g., CRP, WCC) from day 0 to day 3
  • Safety Issue?: Yes
• Change in alveolar PO2-arterial PO2 (A-a) gradient (on air) on day 0 and day 3
  • Safety Issue?: Yes
• Continuous oximetry monitoring from day 0 to day 3 (on air unless saturation < 90%)
  • Safety Issue?: Yes
• Average conscious level measured by Glasgow Coma scale from day 0 to day 3
  • Safety Issue?: Yes
• Drug- and talc-related adverse reactions
  • Safety Issue?: Yes
• Complications from chest drain insertion
  • Safety Issue?: Yes
• Presence of chronic chest wall pain assessed at all follow-up visits
  • Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Oxford Radcliffe Hospital

Overall Clinical Trial Officials and Contacts

Robert Davies, MD Principal Investigator Oxford Radcliffe Hospital  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00644319

Study ID Number: CDR0000590072

ClinicalTrials.gov Identifier: NCT00644319

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database