Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Supportive care, Treatment	Active	18 and over	Other	RADCLIFFE-TIME1 TIME1, ISRCTN33288337, EUDRACT 2006-005226-31, EU-20829, UKCRN 4035, NCT00644319

Objectives

Primary

1. 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.
2. To evaluate whether chest drain size influences the amount of post-pleurodesis pain.

Entry Criteria

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

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

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

Expected Enrollment

Outcomes

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)

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

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.

Trial Contact Information

Trial Lead Organizations

Oxford Radcliffe Hospital

Robert Davies, MD, Principal investigator		Ph: 44-186-522-5205

United Kingdom
England
	Oxford
	Oxford Radcliffe Hospital
		Contact Person	Ph:  44-1865-225-205
			Email: robert.davies@ndm.ox.ac.uk

Registry Information
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]
Trial Start Date		2007-03-26
Trial Completion Date		2009-09-30 (estimated)
Registered in ClinicalTrials.gov		NCT00644319
Date Submitted to PDQ		2008-03-12
Information Last Verified		2008-11-30