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

Condition(s) targeted: Metastatic Cancer

Intervention: ibuprofen (Drug); morphine sulfate (Drug); management of therapy complications (Procedure); pleurodesis (Procedure)

Phase: Phase 2

Status: Recruiting

Sponsored by: Oxford Radcliffe Hospital

Official(s) and/or principal investigator(s):
Robert Davies, MD, Principal Investigator, Affiliation: Oxford Radcliffe Hospital

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.

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]

Study design: Supportive Care, Randomized

Primary outcome:

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:

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

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

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

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

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

Starting date: March 2007
Last updated: July 7, 2009