Clinical trial NCT01612975: The Effect of Non-Steroidal Anti-Inflammatory Drug Naproxen on Pleural Effusion Formation After Lung Resection
Official title: The Effect of Perioperative Non-Steroidal Anti-Inflammatory Drug Naproxen on Pleural Effusion Formation After Lung Resection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pleural Effusion
Pleural Effusion Malignant
Keywords: Chest tubes
Length of stay
Pleural effusion
Lung resection
Post-operative
Lung cancer
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: McMaster Surgical Associates
First posted: 2012-06-06
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Following a lung resection procedure, patients have their pleural space drained of fluid that accumulates due to the severing of proximal vessels like lymph nodes. The volume of fluid pumped depends on the severity of the inflammation. The investigators are conduction this study to attempt to use painkillers with intrinsic anti-inflammatory action to try and reduce the degree of inflammation in patients' pleural cavity, thus ensuring patients are discharged faster, with a greater comfort level, and a hopefully lower rate of admission.

Detailed description: In this study the investigators will attempt to reduce the degree of inflammation (and thus polymorphonuclear leukocyte counts) in the pleural space following a lung resection procedure by administering the Non Steroid Anti-Inflammatory Drug (NSAID) Naproxen in tandem with Proton Pump Inhibitor (PPI) Pantoprazole, ideally leading towards a significantly reduced volume of transudate and exudate generated.

This will be achieved by running a placebo-controlled double blinded randomized control trial where investigators and participants will be blinded so as to eliminate experimenter bias. After screening for suitable participants using stringent inclusion and exclusion criteria, patients will be administered by allied health professionals 500mg Naproxen twice daily and 40mg Pantoprazole once daily, or an identical placebo for four weeks following resection surgery. Patients will undergo a thorough examination during their scheduled follow-up appointments to monitor general vitals as well as possible gastrointestinal complications. The primary outcome is a significant reduction (Δ100ml) of chest fluid extracted in the intervention arm of the study in comparison to that of the control arm. Secondary outcomes will include a reduction in length of stay measured in days between control and intervention arms as well as a reduction in the total number of days chest tubes are retained in-situ. Conditions such as mortality and morbidity, the onset of complications, and general re-admission rates will also be recorded.

Eligibility criteria: Inclusion Criteria:

* Participants must be 18 years of age or older
* Participants must be undergoing a major lung resection due to primary or secondary malignancy
* Must have an aptitude for following directions and commitment to the study

Exclusion Criteria:

* Patients who are unable to read and communicate in English
* Patients undergoing a pneumonectomy or Open lung resection
* Previous treatments on the same anatomical side including chemotherapy, radiation therapy, and radio-frequency ablation
* Patients who have undergone decortication for empyema or malignancy.
* Patients who have a chest tube in-situ for persistent air leak
* Patients with clinical or laboratory indicators of renal failure, defined as serum creatinine level of 170µmol/l
* Patients with active or previous history of peptic ulcer disease
* Patients with a known intolerance to Proton Pump Inhibitors (PPIs)
* Known allergy to study drugs
* Use of NSAIDs 4 weeks prior to randomization or on-going use of NSAIDs.
* The use of any medications known to reduce inflammation, including but not limited to: steroids (both oral and intravenously), methotrexate, COX-II inhibitors, other NSAIDs
* Chest tube for persistent air leak.
* Patients who are pregnant or lactating
* Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
* Inability or unwillingness of individual or legal guardian/representative to give written informed consent

Primary outcomes:
measure: Change in volume of pleural effusion collected
timeFrame: 4 weeks
Secondary outcomes:
measure: Hospital length of stay; compared between intervention and control arms
timeFrame: 4 weeks
measure: Gastrointestinal complications
timeFrame: 4 weeks
measure: General re-admission rates
timeFrame: 4 weeks
measure: Total number of days chest tubes remain in-situ
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
Study officials:
affiliation: McMaster University
name: Yaron Shargall, MD, BSc, FRCSC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Watanabe A, Watanabe T, Ohsawa H, Mawatari T, Ichimiya Y, Takahashi N, Sato H, Abe T. Avoiding chest tube placement after video-assisted thoracoscopic wedge resection of the lung. Eur J Cardiothorac Surg. 2004 May;25(5):872-6. doi: 10.1016/j.ejcts.2004.01.041.
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citation: Scheiman JM, Hindley CE. Strategies to optimize treatment with NSAIDs in patients at risk for gastrointestinal and cardiovascular adverse events. Clin Ther. 2010 Apr;32(4):667-77. doi: 10.1016/j.clinthera.2010.04.009.
citation: Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, Egger M, Juni P. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011 Jan 11;342:c7086. doi: 10.1136/bmj.c7086.
citation: Ackerman N, Tomolonis A, Miram L, Kheifets J, Martinez S, Carter A. Three day pleural inflammation: a new model to detect drug effects on macrophage accumulation. J Pharmacol Exp Ther. 1980 Dec;215(3):588-95.