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

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 Overview

• Status: Unknown
• Conditions: Metastatic Cancer
• Intervention / Treatment: Procedure: management of therapy complications; Drug: ibuprofen; Drug: morphine sulfate; Procedure: pleurodesis

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 320
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • Oxford, England, United Kingdom, 0X3 9DU
      • Recruiting
      • Oxford Radcliffe Hospital
      • Contact: Contact Person; Phone Number: 44-1865-225-205; Email: robert.davies@ndm.ox.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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
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

Collaborators and Investigators

• Sponsor: Oxford University Hospitals NHS Trust
• Investigators: Principal Investigator: Robert Davies, MD, Oxford University Hospitals NHS Trust

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (ANTICIPATED): September 1, 2009

Study Registration Dates

• First Submitted: March 25, 2008
• First Submitted That Met QC Criteria: March 25, 2008
• First Posted (ESTIMATE): March 26, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): July 8, 2009
• Last Update Submitted That Met QC Criteria: July 7, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: malignant pleural effusion
• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Analgesics, Opioid; Narcotics; Morphine; Ibuprofen
• Other Study ID Numbers: CDR0000590072; RADCLIFFE-TIME1; ISRCTN33288337; EUDRACT 2006-005226-31; EU-20829; UKCRN 4035