The Effect of Non-Steroidal Anti-Inflammatory Drug Naproxen on Pleural Effusion Formation After Lung Resection

The Effect of Perioperative Non-Steroidal Anti-Inflammatory Drug Naproxen on Pleural Effusion Formation After Lung Resection

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.

Study Overview

• Status: Terminated
• Conditions: Pleural Effusion; Pleural Effusion Malignant
• Intervention / Treatment: Drug: Placebo; Drug: Naproxen

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; This study arm will encompass the administration of a placebo (physically identical to Naproxen) orally to participants. Naproxen is a painkiller with intrinsic anti-inflammatory properties, while the placebo has no pharmacological properties associated with it. Participants will also be taking Pantoprazole to negate the gastrointestinal consequences of Naproxen (or the placebo). Participants will not know which arm of the study they belong to. In addition, they will attend scheduled check-ups where their vitals will be recorded, as well as laboratory indicators of gastrointestinal complications (creatinine levels, etc) for their safety.	Drug: Placebo; Inert, inactive placebo pill similar in appearance to naproxen allocation. To be taken twice daily for 4 weeks total along with 40mg pantoprazole.
EXPERIMENTAL: Naproxen; Intervention arm involves administering 500mg Naproxen twice a day to participants and 40mg of Pantoprazole once a day in tandem. Pantoprazole will negate gastrointestinal consequences of Naproxen and reduce the likelihood of a complication occurring. Participants will take Naproxen at the above dosage from the time of surgery to four weeks following surgery. They will attend scheduled check-ups where their vitals will be recorded, as well as laboratory indicators of gastrointestinal complications (creatinine levels, etc) for their safety. This experiment is double-blinded so neither investigators nor participants will know which arm of the study they belong to.	Drug: Naproxen; Intervention arm involves administering 500mg Naproxen BID to participants and 40mg of Pantoprazole in tandem. Pantoprazole will negate gastrointestinal consequences of Naproxen and reduce the likelihood of a complication occurring. Participants will take Naproxen at the above dosage from the time of surgery to four weeks following surgery. They will attend scheduled check-ups where their vitals will be recorded, as well as laboratory indicators of gastrointestinal complications (creatinine levels, etc) for their safety. This experiment is double-blinded so neither investigators nor participants will know which arm of the study they belong to.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in volume of pleural effusion collected	The investigators are looking to measure the volume of pleural effusion collected from in-situ chest tubes in patients following a lung resection, measured in mL	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital length of stay; compared between intervention and control arms	The length of stay will be measured from the admitting day to the day of discharge to home.	4 weeks
Gastrointestinal complications	Recorded as a binary event, adverse events related to the gastrointestinal tract may occur in participants undergoing treatment. The extent of this occurrence will determine whether or not further intervention by the Data and Safety Monitoring Committee is necessary.	4 weeks
General re-admission rates	Participants recently discharged following a lung resection have a chance to be re-admitted for a post-operative complication. This will be measured as a binary event and the total associated length of stay associated with the episode.	4 weeks
Total number of days chest tubes remain in-situ	This outcome is related to the volume of pleural effusion produced and will measure the time chest tubes remain in place following surgery, measured in days.	4 weeks

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: McMaster Surgical Associates
• Investigators: Principal Investigator: Yaron Shargall, MD, BSc, FRCSC, McMaster University

Publications and helpful links

General Publications

• 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.
• Cerfolio RJ, Bryant AS. Results of a prospective algorithm to remove chest tubes after pulmonary resection with high output. J Thorac Cardiovasc Surg. 2008 Feb;135(2):269-73. doi: 10.1016/j.jtcvs.2007.08.066.
• Suemitsu R, Ondo K, Fukuyama S, Ueda H. Late-period-onset chylothorax after a pulmonary resection for lung cancer: a case report. Ann Thorac Cardiovasc Surg. 2007 Oct;13(5):345-8.
• Kroegel C, Antony VB. Immunobiology of pleural inflammation: potential implications for pathogenesis, diagnosis and therapy. Eur Respir J. 1997 Oct;10(10):2411-8. doi: 10.1183/09031936.97.10102411.
• 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.
• 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.
• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (ACTUAL): January 1, 2018
• Study Completion (ACTUAL): January 1, 2018

Study Registration Dates

• First Submitted: June 4, 2012
• First Submitted That Met QC Criteria: June 4, 2012
• First Posted (ESTIMATE): June 6, 2012

Study Record Updates

• Last Update Posted (ACTUAL): February 15, 2018
• Last Update Submitted That Met QC Criteria: February 13, 2018
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Lung cancer; Post-operative; Pleural effusion; Length of stay; Lung resection; Chest tubes
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Pleural Effusion, Malignant; Pleural Effusion; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gout Suppressants; Naproxen
• Other Study ID Numbers: SJHHNaproxenRCT