Trial document





This trial has been registered retrospectively.
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  DRKS00014027

Trial Description

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Title

Biomarkers for predicting postoperative complications following anatomic lung resection

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Trial Acronym

BNP

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URL of the Trial

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Brief Summary in Lay Language

Accurate risk assessment prior to anatomic lung resection is crucial to optimize therapeutic strategies for lung cancer patients. Although the guidelines on risk assessment for major lung resection are widely used in clinical practice, they have relevant limitations and are less reliable in some patient groups, e.g. in those presenting with imparied pulmonary function or considered for minimally invasive approach. In this regard more reliable predictors are needed to improve risk stratification for anatomic lung resection.

In this prospective study, we assess the predictive ability of B-type natriuretic peptide (BNP) and lactate for postoperative complications after anatomic lung resection. The study is currently enrolling adult patients with confirmed or suspected lung cancer, who are considered for anatomic lung resection. The predictive abilities of BNP and lactate will be examined by means of multivariable analyses. This study may result in more precise risk stratification prior to surgery and improve tailored lung cancer treatment for individual patients.

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Brief Summary in Scientific Language

Despite the advance in the non-surgical therapy modalities, anatomic lung resection remains the therapy of choice for early-stage non-small cell lung cancer (NSCLC) due to the favorable oncological outcomes and survival rates [1, 2]. Accurate risk assessment is crucial to optimize therapeutic strategies for lung cancer patients[3]. In the current clinical guidelines, pulmonary function determinants are widely used predictors of postoperative complications after lobectomy, including forced expiratory volume in the first second expressed as a percent predicted (FEV1%), diffusing capacity for carbon monoxide expressed as a percent predicted (DLCO%) and more powerfully their predicted postoperative values (ppoFEV1%, ppoDLCO%) [4,5]. However, in patients with compromised pulmonary function ppoFEV1% has becomen less reliable in predicting postoperative morbidity [6-8]. It is postulated that the pulmonary function in this patient population is less lost, or even improved after major lung resection (lung volumen reduction effect) [6,7,9].

In the last decade thoracoscopic lobectomy has been increasingly used for treating early-stage lung cancer [10,11]. Due to its minimally invasive nature, thoracoscopic lobectomy is associated with better preservation of lung function in the postoperative period [12]. This fact, in turn, might challenge the current risk assessment algorithms [13,14].

B-type natriuretic peptide (BNP) is a prohormone secreted by ventricular cardiomyocytes in response to ischaemia, myocardial stretch, inflammation and other neuroendocrine stimuli [15]. In thoracic surgery preoperative BNP level has been reported to be an independent risk factor for postoperative atrial fibrillation and for cardiopulmonary complications in aged patients [16-19]. In a recent prospective observational cohort study involving 294 patients presenting with normal pulmonary function, postoperative BNP elevation was the strongest independent predictor of cardiopulmonary complications after major lung resections [15]. Moreover, clinical study has demonstrated that BNP is strongly assosicated with peak oxygen uptake (VO2max), which has proven to be best predictor of postoperative complications after lobectomy [20].

Another promising biomarker is serum lactate, which indicates commonly tissue hypoperfusion and hypoxia. Recently pre- and postoperative serum lactate levels were found highly predictive of respiratory complications after lung resection in a prospective study involving 149 patients [21].

In the present prospective study, we measure BNP and lactate and evaluate the clinical outcomes of anatomic lung resections. Multivariable analyses assess the predictive ability of BNP and lactate for postoperative complications after anatomic lung resection. This study might result in more precise risk stratification prior to surgery and improve tailored treatment for lung cancer patients.

References
1. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. The Annals of thoracic surgery. 1995;60(3):615-22; discussion 22-3.
2. Howington JA, Blum MG, Chang AC, Balekian AA, Murthy SC. Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):e278S-313S.
3. Egenlauf B, Herth FJ, Kappes J. [Preoperative pulmonary function analysis and cardiorespiratory risk assessment: the current standard]. Zentralbl Chir 2014; 139 Suppl 1: S6-12.
4. Brunelli A. Algorithm for functional evaluation of lung resection candidates: time for reappraisal? Respiration 2009; 78: 117-118.
5. Ferguson M, Vigneswaran WT. Diffusing capacity predicts morbidity after lung resection in patients without obstructive lung disease. Ann Thorac Surg. 2008; 85: 1158-1164.
6. Seok Y, Jheon S, Cho S. Serial changes in pulmonary function after video-assisted thoracic surgery lobectomy in lung cancer patients. Thorac Cardiovasc Surg 2014; 62: 133-139.
7. Varela G, Brunelli A, Rocco G et al. Predicted versus observed FEV1 in the immediate postoperative period after pulmonary lobectomy. Eur J Cardiothorac Surg 2006; 30: 644-648.
8. Taylor MD, LaPar DJ, Isbell JM et al. Marginal pulmonary function should not preclude lobectomy in selected patients with non-small cell lung cancer. J Thorac Cardiovasc Surg 2014; 147: 738-744; Discussion 744-736.
9. D'Amico TA, Niland J, Mamet R et al. Efficacy of mediastinal lymph node dissection during lobectomy for lung cancer by thoracoscopy and thoracotomy. Ann Thorac Surg 2011; 92: 226-231; discussion 231-222.
10. Su S, Scott WJ, Allen MS et al. Patterns of survival and recurrence after surgical treatment of early stage non-small cell lung carcinoma in the ACOSOG Z0030 (ALLIANCE) trial. J Thorac Cardiovasc Surg 2014; 147: 747-752: Discussion 752-743.
11. Flores RM, Park BJ, Dycoco J et al. Lobectomy by video-assisted thoracic surgery (VATS) versus thoracotomy for lung cancer. J Thorac Cardiovasc Surg 2009; 138: 11-18.
12. Paul S, Altorki NK, Sheng S et al. Thoracoscopic lobectomy is associated with lower morbidity than open lobectomy: a propensity-matched analysis from the STS database. J Thorac Cardiovasc Surg 2010; 139: 366-378.
13. Berry MF, Villamizar-Ortiz NR, Tong BC et al. Pulmonary function tests do not predict pulmonary complications after thoracoscopic lobectomy. Ann Thorac Surg 2010; 89: 1044-1051; discussion 1051-1042.
14. Zhang R, Lee SM, Wigfield C et al. Lung function predicts pulmonary complications regardless of the surgical approach. Ann Thorac Surg 2015; 99: 1761-1767.
15. Cagini L, Andolfi M, Leli C et al. B-type natriuretic peptide following thoracic surgery: a predictor of postoperative cardiopulmonary complications. Eur J Cardiothorac Surg 2014; 46: e74-80.
16. Amar D, Zhang H, Shi W et al. Brain natriuretic peptide and risk of atrial fibrillation after thoracic surgery. J Thorac Cardiovasc Surg 2012; 144: 1249-1253.
17. Cardinale D, Colombo A, Sandri MT et al. Increased perioperative N-terminal pro-B-type natriuretic peptide levels predict atrial fibrillation after thoracic surgery for lung cancer. Circulation 2007; 115: 1339-1344.
18. Nojiri T, Inoue M, Yamamoto K et al. B-type natriuretic Peptide as a predictor of postoperative cardiopulmonary complications in elderly patients undergoing pulmonary resection for lung cancer. Ann Thorac Surg 2011; 92: 1051-1055.
19. Nojiri T, Maeda H, Takeuchi Y et al. Predictive value of B-type natriuretic peptide for postoperative atrial fibrillation following pulmonary resection for lung cancer. Eur J Cardiothorac Surg 2010; 37: 787-791.
20. Krüger S, Graf J, Kunz D et al. Brain natriuretic peptide levels predict functional capacity in patients with chronic heart failure.J Am Coll Cardiol. 2002;40:718-22.
21. Tsagkaropoulos S, Sileli M, Ampatzidou F et al. Value of serum lactate kinetics after lung resection. In 22nd European Conference on General Thoracic Surgery. Copenhagen, Denmark: 2014.

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Organizational Data

  •   DRKS00014027
  •   2018/03/02
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  •   yes
  •   Approved
  •   019/2016BO2, Ethik-Kommission an der Medizinischen Fakultät der Eberhard-Karls-Universität und am Universitätsklinikum Tübingen
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Secondary IDs

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Health Condition or Problem studied

  •   C34 -  Malignant neoplasm of bronchus and lung
  •   In this prospective study we assess the predictive ability of B-type natriuretic peptide (BNP) and lactate for complications after anatomic lung rescection.
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Interventions/Observational Groups

  •   Patients undergoing anatomic lung resection including pneumonectomy, lobectomy, Bi-lobectomy and segmentectomy.

    Serum BNP is measured at three different time points: preoperatively, shortly after the surgery (within 1 hour) and on postoperative day 1. Lactate is measured in arterial blood samples at four different time points: preoperatively, shortly after the surgery (within 1 hour), 3 and 6 hours after surgery. Complications following anatomic lung resection are evaluated in the postoperative period and in the follow-ups 6 weeks and 6 months after surgery.
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Characteristics

  •   Non-interventional
  •   Other
  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Prognosis
  •   Single (group)
  •   N/A
  •   N/A
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Primary Outcome

The primary outcome is the cardiopulmonary complication 6 months following anatomic lung resection. Patient follow-up is carried out 6 weeks and 6 months following anatomic lung resection in the out-patient department.

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Secondary Outcome

The secondary outcome is the overall morbidity 6 months following anatomic lung resection. Patient follow-up is carried out 6 weeks and 6 months following anatomic lung resection in the out-patient department.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
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Recruitment

  •   Actual
  •   2016/11/22
  •   400
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

Patients with confirmed or suspected lung cancer, who undergo anatomic lung resektion (pneumonectomy, lobectomy, Bi-lobectomy or segmentectomy) as elective surgery.

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Exclusion Criteria

1. Lack of willingness to participate or capacity for consent,
2. Urgent or emergency surgery,
3. Redo surgery,
4. Age < 18,
5. Angina pectoris, myocardial infarction, pulmonary oedema, stroke or pneumonia in the last months.

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Addresses

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    • Abteilung für Thoraxchirurgie,Klinik Schillerhöhe,Robert-Bosch-KrankenhausProf. Dr. med. Godehard Friedel, Dr. med. Ruoyu Zhang
    • Mr. 
    • 70839  Gerlingen/Stuttgart
    • Germany
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    • Abteilung für ThoraxchirurgieKlinik Schillerhöhe, Robert-Bosch-Krankenhaus
    • Mr.  Dr. med.  Ruoyu  Zhang 
    • Solitudestrasse 18
    • 70839  Gerlingen/Stuttgart
    • Germany
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    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address scientific-contact
    • Abteilung für ThoraxchirurgieKlinik Schillerhöhe, Robert-Bosch-Krankenhaus
    • Mr.  Professor  Godehard  Friedel 
    • Solitudestrasse 18
    • 70839  Gerlingen/Stuttgart
    • Germany
    end of 1:1-Block address scientific-contact
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    end of 1:1-Block address contact scientific-contact
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    • Abteilung für ThoraxchirurgieKlinik Schillerhöhe, Robert-Bosch-Krankenhaus
    • Mr.  Dr. med.  Ruoyu  Zhang 
    • Solitudestrasse 18
    • 70839  Gerlingen/Stuttgart
    • Germany
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Sources of Monetary or Material Support

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    • Kommission Klinischer Forschung, Robert-Bosch-Krankenhaus
    • Mr.  Professor  Mark Dominik  Alscher 
    • Postfach 501120
    • 70341  Stuttgart
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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