Intrapleural Minocycline After Simple Aspiration for the Prevention of Primary Spontaneous Pneumothorax
|ClinicalTrials.gov Identifier: NCT00418392|
Recruitment Status : Unknown
Verified November 2012 by National Taiwan University Hospital.
Recruitment status was: Recruiting
First Posted : January 4, 2007
Last Update Posted : December 17, 2012
|First Submitted Date ICMJE||December 31, 2006|
|First Posted Date ICMJE||January 4, 2007|
|Last Update Posted Date||December 17, 2012|
|Study Start Date ICMJE||November 2006|
|Actual Primary Completion Date||April 2012 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||to compare the rates of ipsilateral recurrence between the minocycline and observation groups after simple aspiration of the pneumothorax. [ Time Frame: 12 months after treatment ]|
|Original Primary Outcome Measures ICMJE
||to compare the rates of ipsilateral recurrence between the minocycline and observation groups after simple aspiration of the pneumothorax.|
|Change History||Complete list of historical versions of study NCT00418392 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Intrapleural Minocycline After Simple Aspiration for the Prevention of Primary Spontaneous Pneumothorax|
|Official Title ICMJE||Intrapleural Minocycline After Simple Aspiration for the Prevention of Primary Spontaneous Pneumothorax: A Randomized Trial|
The estimated recurrence rate of primary spontaneous pneumothorax is 23-50% after the first episode, and the optimal treatment remains unknown. In the recently published British Thoracic Society (BTS) guidelines, simple aspiration is recommended as first line treatment for all primary pneumothoraces requiring intervention. However, the 1 year recurrence rate of this procedure was as high as 25-30%, making it inappropriate as a standard of care.
Intrapleural instillation of a chemical irritant (chemical pleurodesis) is an effective way to shorten the duration of air leaks and reduce the rates of recurrent spontaneous pneumothorax in surgical and non-surgical patients. Many chemical irritants (tetracycline, talc, and minocycline) have been used to decrease the rate of recurrence in spontaneous pneumothorax. Tetracycline, which was the most commonly used irritant, is no longer available. Talc insufflation of the pleural cavity is safe and effective for primary spontaneous pneumothorax. However, it should be applied either with surgical or medical thoracoscopy. Minocycline, a derivative of tetracycline, is as effective as tetracycline in inducing pleural fibrosis in rabbits. In the previous studies, we have shown that additional minocycline pleurodesis is a safe and convenient procedure to decrease the rates of ipsilateral recurrence after thoracoscopic treatment of primary spontaneous pneumothorax. In the present study, additional minocycline pleurodesis will be randomly administered in patients with first episode of primary spontaneous pneumothorax after simple aspiration to test if it can reduce the rate of recurrence.
Primary spontaneous pneumothorax most commonly occurs in young, tall, lean males (1, 2). The estimated recurrence rate is 23-50% after the first episode (3). Optimal treatment of patients presenting with a first episode of primary spontaneous pneumothorax remains unknown. In the recently published British Thoracic Society (BTS) guidelines (4), simple aspiration is recommended as first line treatment for all primary pneumothoraces requiring intervention. However, the 1 year recurrence rate of this procedure was as high as 26-30% (5), making it inappropriate as a standard of care.
Intrapleural instillation of a chemical irritant (chemical pleurodesis) is an effective way to shorten the duration of air leaks and reduce the rates of recurrent spontaneous pneumothorax in surgical and non-surgical patients (6, 7). Light et al. has shown that intrapleural tetracycline is effective in reducing the rate of ipsilateral recurrence for patients with spontaneous pneumothorax (7). However, the recently published guidelines recommended that chemical pleurodesis should only be attempted if the patient is either unwilling or unable to undergo surgery because the rates of recurrence of pneumothoraces after surgical intervention either by thoracotomy or VATS, with or without surgical pleurodesis, is far less than after chemical pleurodesis (4, 8). As a result, chemical pleurodesis has rarely been used in primary spontaneous pneumothorax, and the effect of additional chemical pleurodesis after simple aspiration in preventing recurrence of pneumothoraces has never been evaluated.
Tetracycline, which was the most commonly used irritant, is no longer available. Minocycline, a derivative of tetracycline, is as effective as tetracycline in inducing pleural fibrosis in rabbits (9). In the previous studies, we have shown that additional minocycline pleurodesis is a safe and convenient procedure that associates with lower rates of prolonged air leaks and ipsilateral recurrence after thoracoscopic treatment of primary spontaneous pneumothorax (10, 11).
In the present study, additional minocycline pleurodesis will be randomly administered in patients with first episode of primary spontaneous pneumothorax after simple aspiration to test if it can reduce the rate of recurrence. This study will comply with the protocol, GCP and applicable requirement of the Institutional Review Boards (IRB) of the NTUH and Far Eastern Memorial Hospital.
Patients and Methods:
Study design This study is a prospective, randomized, controlled trial to evaluate if additional minocycline pleurodesis after simple aspiration will be effective in preventing recurrence of primary spontaneous pneumothorax.
Primary Objective The primary end point is to compare the rates of ipsilateral recurrence between the minocycline and observation groups after simple aspiration of the pneumothorax.
Patients must meet ALL of the inclusion criteria for the entry of this study:
The exclusion criteria are:
Patients will be randomized at each center with separate random number lists into one of the two treatment groups using a computer-generated table numerically corresponding with the treatment group. The trial treatment randomization codes will be maintained until the end of the study and will be broken by investigators who were blind to the randomization procedure.
Manual aspiration Manual aspiration will be performed as follows: patients were seated in semi-supine position. After skin disinfection and field preparation, a small-caliber pig-tail catheter (6-10 French) will be introduced after local anesthesia with 2% lidocaine in the second intercostal space, at the midclavicular line. After the catheter enters the pleural space, the catheter will be fixed to the skin using sterile adhesive tape and connected via a three-way valve to a 50-ml syringe. Air will be manually aspirated, until a resistance was felt and air was no longer aspirated. Thereafter, a chest X-ray will be performed with the catheter in place.
Minocycline pleurodesis In the minocycline group, 30 mL of 1% lidocaine hydrochloride (300mg) followed by a solution of 30 mL of normal saline containing 300 mg of minocycline (Mirosin®, Taiwan Panbiotic Laboratories, Kaohsiung, Taiwan) will be instilled into the pleural cavity through the pig-tail catheter or chest tube. In the observation group, nothing will be administered. Administration of other chemical pleurodesis agents is prohibited during the study period. Intramuscular meperidine hydrochloride (Demerol®, 50mg/ampule) will be administered every 4 to 6 hours according to the patient's request if the pain became intolerable, could not be relieved by oral analgesics, and visual analogue scale was greater than 7. Chest radiography will be performed immediate postoperatively or the next morning. VAS will be evaluated immediately 6 hours later after minocycline administration.
The primary end point will be rate of ipsilateral recurrence after the procedure. Secondary end points include safety, early results, and long-term effects of minocycline pleurodesis.
Immediate success rates: defined as complete or nearly complete and persistent lung expansion immediately following manual aspiration. Immediate success for chest tube drainage is defined as complete lung expansion, absence of air leakage, and chest drain removal within 24 hours after catheter placement.
One weeks success rates are defined as complete and persistent lung expansion at one weeks after the first attempt of aspiration or tube insertion.
One-year success: absence of recurrent pneumothorax during a 1-year follow-up period. .
Safety assessments will consist of monitoring and recording all toxicity, adverse events, safety laboratory examination, vital signs, physical examination. The adverse events which are not reported will be graded as mild, moderate, severe, and life-threatening. Adverse event will be tabulated and the incidence rates will be calculated.
Sample size estimation:
A sample size of 300 patients (150 in each group) will be needed to reach clinical significance (at the .05 level with a power of 0.9) if minocycline reduced the recurrence rate from 30% to 15% and the drop out rate is 10%. A planned interim analysis will be conducted after enrollment of 150 patients with at least 12 months of follow-up. Statistical analysis will be performed on an intent-to-treat basis rather than in an actual treatment basis.
Follow-up After discharge from the hospital, patients will be followed at the outpatient clinics at 1 week, 1 month, 3 months, and 6 months where chest radiography will be performed. Follow-ups will then be conducted every 6 months by a registered nurse who is blinded to the group allocation by telephone conversation, according to a standard questionnaire that included when the patient returns to work or school, whether a recurrence occurred, when it happened, and how it is treated. Residual postoperative chest pain will be evaluated on a pain score from 0 to 5, where 0 is pain free; 1 is occasional discomfort; 2 is occasional use of analgesics; 3 is using nonopiate analgesics; 4 is regular pain using opiates; 5 is severe and intractable pain. All patients will be followed for at least 12 months. Patients can come back to the clinic or visit emergency department whenever they have chest pain, dyspnea, or any signs related to the recurrence of pneumothorax.
Pulmonary function analysis Pulmonary function tests will be performed for patients able to attend a hospital outpatient appointment at least 6 months after surgery. Forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1.0) will be measured using a spirometer of Microspiro HI-298 (Chest Corporation, Tokyo, Japan) with the patients seated. A minimum of three acceptable forced expiratory maneuvers will be performed and the best one will be selected for analysis.
Data collection and statistical analysis The clinical data, duration of chest drainage, length of hospital stay, complications, requested doses of meperidine, and data of VAS will be collected. Continuous variables such as age or weight will be expressed as the mean + standard deviation and analyzed by the two sample t-test. Categorical variables such as gender or smoking status will be presented by frequency (%) and analyzed by the Fisher's exact test. Intensity of postoperative pain measured by VAS (from 0 to 10) were summarized by mean (95 percent confidence interval) and compared by Wilcoxon rank-sum test. Scores of residual chest pain will be analyzed by the Wilcoxon rank-sum test. Freedom from recurrence will be analyzed by the Kaplan-Meier method, and comparisons will be made by the log-rank test.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Estimated Enrollment ICMJE
|Original Enrollment ICMJE||Same as current|
|Estimated Study Completion Date||December 2012|
|Actual Primary Completion Date||April 2012 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||15 Years to 40 Years (Child, Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Taiwan|
|Removed Location Countries|
|NCT Number ICMJE||NCT00418392|
|Other Study ID Numbers ICMJE||950510
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Taiwan University Hospital|
|Study Sponsor ICMJE||National Taiwan University Hospital|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Taiwan University Hospital|
|Verification Date||November 2012|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP