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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified July 2009 by National Cancer Institute (NCI).
Recruitment status was:  Recruiting
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: March 25, 2008
Last updated: July 7, 2009
Last verified: July 2009

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.

Condition Intervention Phase
Metastatic Cancer
Drug: ibuprofen
Drug: morphine sulfate
Procedure: management of therapy complications
Procedure: pleurodesis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Supportive Care
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]

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome 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
  • Pleurodesis success at 3 months post randomization (time to relapse of pleural effusion, censored for survival)

Secondary Outcome Measures:
  • 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

Estimated Enrollment: 320
Study Start Date: March 2007
Estimated Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Detailed Description:



  • 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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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
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Please refer to this study by its identifier: NCT00644319

United Kingdom
Oxford Radcliffe Hospital Recruiting
Oxford, England, United Kingdom, 0X3 9DU
Contact: Contact Person    44-1865-225-205   
Sponsors and Collaborators
Oxford University Hospitals NHS Trust
Principal Investigator: Robert Davies, MD Oxford University Hospitals NHS Trust
  More Information Identifier: NCT00644319     History of Changes
Other Study ID Numbers: CDR0000590072
EUDRACT 2006-005226-31
UKCRN 4035
Study First Received: March 25, 2008
Last Updated: July 7, 2009

Keywords provided by National Cancer Institute (NCI):
malignant pleural effusion

Additional relevant MeSH terms:
Pleural Effusion
Neoplasm Metastasis
Pleural Effusion, Malignant
Pleural Diseases
Respiratory Tract Diseases
Neoplastic Processes
Pathologic Processes
Pleural Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on May 22, 2017