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

Purpose

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.

Condition	Intervention	Phase
Pleural Effusion Pleural Effusion Malignant	Drug: Naproxen Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	The Effect of Perioperative Non-Steroidal Anti-Inflammatory Drug Naproxen on Pleural Effusion Formation After Lung Resection

Resource links provided by NLM:

Drug Information available for: Naproxen Naproxen sodium Pantoprazole Pantoprazole sodium

U.S. FDA Resources

Further study details as provided by McMaster University:

Primary Outcome Measures:

Change in volume of pleural effusion collected [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
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

Secondary Outcome Measures:

Hospital length of stay; compared between intervention and control arms [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
The length of stay will be measured from the admitting day to the day of discharge to home.
Gastrointestinal complications [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
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.
General re-admission rates [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
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.
Total number of days chest tubes remain in-situ [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
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.

Estimated Enrollment:	300
Study Start Date:	January 2013
Estimated Study Completion Date:	February 2014
Estimated Primary Completion Date:	January 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 and will receive their medication from the SJHH pharmacy. 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 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.	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.

Arms

Assigned Interventions

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 and will receive their medication from the SJHH pharmacy. 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 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.

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.

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 BID and 40mg Pantoprazole QD, 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

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Participants must be between 18 and 80 years of age
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 VATS 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01612975

Contacts

Contact: Laura Schneider, BSc

905-522-1155 ext 35877

lschnei@mcmaster.ca

Locations

Canada, Ontario
St. Joseph's Healthcare Hamilton	Not yet recruiting
Hamilton, Ontario, Canada, L8N 4A6
Principal Investigator: Yaron Shargall, MD FRCSC
Sub-Investigator: Christian J Finley, MD MPH FRCSC
Sub-Investigator: John D Miller, MD FRCSC
Sub-Investigator: Colin Schieman, MD FRCSC

Sponsors and Collaborators

McMaster University

McMaster Surgical Associates

Investigators

Principal Investigator:

Yaron Shargall, MD, BSc, FRCSC

McMaster University

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

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.

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.

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. Review.

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.

Responsible Party:	McMaster University
ClinicalTrials.gov Identifier:	NCT01612975 History of Changes
Other Study ID Numbers:	SJHHNaproxenRCT
Study First Received:	June 4, 2012
Last Updated:	January 21, 2013
Health Authority:	Canada: Health Canada Canada: Ethics Review Committee

Keywords provided by McMaster University:

Chest tubes
Length of stay
Pleural effusion

Lung resection
Post-operative
Lung cancer

Additional relevant MeSH terms:

Pleural Effusion
Pleural Effusion, Malignant
Pleural Diseases
Respiratory Tract Diseases
Pleural Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Naproxen
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Pantoprazole
Analgesics, Non-Narcotic
Analgesics

Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antirheumatic Agents
Gout Suppressants
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents
Proton Pump Inhibitors
Anti-Ulcer Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on June 17, 2013