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

Metastatic Cancer Clinical Trial

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]

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00644319
• Other study ID #: CDR0000590072
• Secondary ID: RADCLIFFE-TIME1I
• Status: Recruiting
• Phase: Phase 2
• First received: March 25, 2008
• Last updated: July 7, 2009
• Start date: March 2007

Study information

• Verified date: July 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Pleural Effusion
• Pleural Effusion, Malignant

Intervention

Drug:
• ibuprofen

• morphine sulfate

Procedure:
• management of therapy complications

• pleurodesis

Locations

Country	Name	City	State
United Kingdom	Oxford Radcliffe Hospital	Oxford	England

Sponsors (1)

Lead Sponsor	Collaborator
Oxford University Hospitals NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

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