Time of Ventilation and Lung Function of Ventilated Patients Under Therapy With Dornase Alfa

Long Term Ventilation Clinical Trial

Official title:

Beatmungsdauer Und Lungenfunktion Bei Beatmeten Patienten Unter Therapie Mit Dornase Alfa - Randomisierte, Doppel-Blinde, Placebo-Kontrollierte, Multizentrische, Prospektive Klinische Studie

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00204685
• Other study ID #: LUFIT
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• First received: September 9, 2005
• Last updated: September 13, 2006
• Start date: August 2003
• Est. completion date: July 2006

Study information

• Verified date: September 2006
• Source: University Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether Inhalation of Recombinant Human Deoxyribonuclease Shortens Ventilation Time in Mechanically Ventilated Adults

Description:

Recombinant human deoxyribonuclease I (rhDNase, dornase alpha), administered by inhalation, is currently used as a mucolytic agent in the treatment of cystic fibrosis. This prospective, randomized, placebo-controlled, double-blind clinical study should carry out whether the therapeutic use of rhDNase can be extended to adults who are undergoing long term ventilation at the intensive care. It is hypothesized that mechanically ventilated patients show elevated concentrations of DNA in airway secretions, and that these pathological DNA levels are reduced by rhDNase. The primary clinical goal of the study is to establish wether ventilation times are shortend under inhalation of rhDNAse during the ventilation time. hDNase (verum) is compared with equal amounts of 0.9% saline solution (placebo).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 540
• Est. completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• adult

• mechanical ventilation

• expected ventilation time 3 days or longer

• full therapy is possible

• expectet ventilation time not longer than 21 days

Exclusion Criteria:

• medicinal point of view: patient won´t survive the next 21 days

• concomitant pneumococcal disease (like tuberculosis, carcinoma)

• endotracheal bleeding

• pneumothorax with no relief (e.g. thoracic drainage)

• pregnancy

• breast feeding

• participation in another clinical trail

• mechanical ventilation since more than 48 hours

• mechanical ventilation on the basis of another reason than operation, trauma or pulmonary decompensation

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Long Term Ventilation

Intervention

Drug:
• dornase alfa

Locations

Country	Name	City	State
Germany	Charité, Universitätsmedizin Berlin, Campus Mitte, Innere Intensivstation	Berlin
Germany	Universität Charité, Campus Mitte, Anästhesie, Intensivstation	Berlin
Germany	Vivantes Klinikum Spandau, Klinik für Anästhesie	Berlin
Germany	Klinikum Chemnitz gGmbH, Innere Medizin	Chemnitz
Germany	Universitätsklinikum Erlangen Medizinische Klinik, Intensivstation I	Erlangen
Germany	Universitätsklinikum, Innere Medizin, Intensivstation	Frankfurt
Germany	Universitätsklinikum Hamburg-Eppendorf, Medizinische Intensivstation	Hamburg
Germany	Medizinische Hochschule Hannover, Anästhesiologie	Hannover
Germany	Anästhesiolog. Klinik der Ruprecht-Karls-Universität	Heidelberg
Germany	Universitätsklinikum des Saarlandes, Innere Medizin III, Internistische Intensivstation	Homburg / Saar
Germany	Klinik für Anästhesiologie u. IntensivtherapieUniversität Leipzig	Leipzig
Germany	Universitätsklinik Lübeck, Medizinische Klinik 1	Lübeck
Germany	Department of internal Medicine	Luedenscheid
Germany	Universität Magdeburg, Innere Medizin,	Magdeburg
Germany	Gutenberg-Universität, Anästhesie-Intensivstation	Mainz
Germany	Johannes Gutenberg-Universität Mainz, II. Medizinische Klinik, Intensivstation	Mainz
Germany	Johannes-Gutenberg-Universität, Neurochirurgische Klinik	Mainz
Germany	Universitätsklinikum Mannheim, I. Med. Klinik	Mannheim
Germany	Klinikum der Philipps-Universität Marburg, Intensivstation III	Marburg
Germany	Klinikum der Univ. München Großhadern	München
Germany	Klinikum der Univ. München Großhadern, Anaesthesiologische Intensivstation	München
Germany	Ludwig Maximilians Universität München, Großhadern, Neurologie-Intensiv	München
Germany	Berufsgenossenschaftliche Klinik Tuebingen, Intensive care Unit	Tuebingen
Germany	Intensive Care Unit of the Internal Department, Universitiy of Tuebingen	Tuebingen
Germany	University Hospital, Anaesthesiology	Tuebingen	Baden-Wuerttemberg

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Tuebingen	Joachim Riethmueller, Dr. med.

Country where clinical trial is conducted

Germany, 

References & Publications (24)

24. Riethmueller J, Grassmé H, Ziebach R, Wessels J, Eyrich M, Stern M, Gulbins E. DNA-quantification and -qualification in sputum of CF-patients for monitoring rhDNase-therapy? Journal of Cystic Fibrosis 1. 6/2002: S110

Aitken ML, Burke W, McDonald G, Shak S, Montgomery AB, Smith A. Recombinant human DNase inhalation in normal subjects and patients with cystic fibrosis. A phase 1 study. JAMA. 1992 Apr 8;267(14):1947-51. — View Citation

Bates RD, Nahata MC. Aerosolized dornase alpha (rhDNase) in cystic fibrosis. J Clin Pharm Ther. 1995 Dec;20(6):313-5. Review. — View Citation

Boeuf B, Prouix F, Morneau S, Marton D, Lacroix J. Safety of endotracheal rh DNAse (Pulmozyme) for treatment of pulmonary atelectasis in mechanically ventilated children. Pediatr Pulmonol. 1998 Aug;26(2):147. — View Citation

Brandt T, Breitenstein S, von der Hardt H, Tümmler B. DNA concentration and length in sputum of patients with cystic fibrosis during inhalation with recombinant human DNase. Thorax. 1995 Aug;50(8):880-2. — View Citation

Cook DJ, Walter SD, Cook RJ, Griffith LE, Guyatt GH, Leasa D, Jaeschke RZ, Brun-Buisson C. Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Ann Intern Med. 1998 Sep 15;129(6):433-40. — View Citation

Dasgupta B, King M. Reduction in viscoelasticity in cystic fibrosis sputum in vitro using combined treatment with nacystelyn and rhDNase. Pediatr Pulmonol. 1996 Sep;22(3):161-6. — View Citation

Desai M, Weller PH, Spencer DA. Clinical benefit from nebulized human recombinant DNase in Kartagener's syndrome. Pediatr Pulmonol. 1995 Nov;20(5):307-8. — View Citation

Durward A, Forte V, Shemie SD. Resolution of mucus plugging and atelectasis after intratracheal rhDNase therapy in a mechanically ventilated child with refractory status asthmaticus. Crit Care Med. 2000 Feb;28(2):560-2. — View Citation

Fuchs HJ, Borowitz DS, Christiansen DH, Morris EM, Nash ML, Ramsey BW, Rosenstein BJ, Smith AL, Wohl ME. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group. N Engl J Med. 1994 Sep 8;331(10):637-42. — View Citation

Grassmé H, Kirschnek S, Riethmueller J, Riehle A, v Kürthy G, Lang F, Weller M, Gulbins E. Role of apoptosis in Pseudomonas aeruginosa pneumonia. Science 194, 11/2001: 1783a

Grassmé H, Kirschnek S, Riethmueller J, Riehle A, von Kürthy G, Lang F, Weller M, Gulbins E. CD95/CD95 ligand interactions on epithelial cells in host defense to Pseudomonas aeruginosa. Science. 2000 Oct 20;290(5491):527-30. — View Citation

Harms HK, Matouk E, Tournier G, von der Hardt H, Weller PH, Romano L, Heijerman HG, FitzGerald MX, Richard D, Strandvik B, Kolbe J, Kraemer R, Michalsen H. Multicenter, open-label study of recombinant human DNase in cystic fibrosis patients with moderate lung disease. DNase International Study Group. Pediatr Pulmonol. 1998 Sep;26(3):155-61. — View Citation

King M, Dasgupta B, Tomkiewicz RP, Brown NE. Rheology of cystic fibrosis sputum after in vitro treatment with hypertonic saline alone and in combination with recombinant human deoxyribonuclease I. Am J Respir Crit Care Med. 1997 Jul;156(1):173-7. — View Citation

Patel A, Harrison E, Durward A, Murdoch IA. Intratracheal recombinant human deoxyribonuclease in acute life-threatening asthma refractory to conventional treatment. Br J Anaesth. 2000 Apr;84(4):505-7. — View Citation

Puchelle E, Zahm JM, de Bentzmann S, Grosskopf C, Shak S, Mougel D, Polu JM. Effects of rhDNase on purulent airway secretions in chronic bronchitis. Eur Respir J. 1996 Apr;9(4):765-9. — View Citation

Reiter PD, Townsend SF, Velasquez R. Dornase alfa in premature infants with severe respiratory distress and early bronchopulmonary dysplasia. J Perinatol. 2000 Dec;20(8 Pt 1):530-4. — View Citation

Rochat T, Pastore FD, Schlegel-Haueter SE, Filthuth I, Auckenthaler R, Belli D, Suter S. Aerosolized rhDNase in cystic fibrosis: effect on leucocyte proteases in sputum. Eur Respir J. 1996 Nov;9(11):2200-6. — View Citation

Shah PL, Conway S, Scott SF, Rainisio M, Wildman M, Stableforth D, Hodson ME. A case-controlled study with dornase alfa to evaluate impact on disease progression over a 4-year period. Respiration. 2001;68(2):160-4. — View Citation

Shah PL, Hodson ME. New treatment strategies in cystic fibrosis: rhDNase. Monaldi Arch Chest Dis. 1996 Apr;51(2):125-9. Review. — View Citation

Shah PL, Scott SF, Knight RA, Marriott C, Ranasinha C, Hodson ME. In vivo effects of recombinant human DNase I on sputum in patients with cystic fibrosis. Thorax. 1996 Feb;51(2):119-25. — View Citation

Touleimat BA, Conoscenti CS, Fine JM. Recombinant human DNase in management of lobar atelectasis due to retained secretions. Thorax. 1995 Dec;50(12):1319-21; discussion 1323. — View Citation

Voelker KG, Chetty KG, Mahutte CK. Resolution of recurrent atelectasis in spinal cord injury patients with administration of recombinant human DNase. Intensive Care Med. 1996 Jun;22(6):582-4. — View Citation

Wills PJ, Wodehouse T, Corkery K, Mallon K, Wilson R, Cole PJ. Short-term recombinant human DNase in bronchiectasis. Effect on clinical state and in vitro sputum transportability. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):413-7. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time of mechanical ventilation from beginning of the ventilation-therapy up to the end of the ventilation-therapy
Secondary	reduction of atelectasis / dystelectasis
Secondary	improval of pulmonaryfunction
Secondary	reduction of pneumonia
Secondary	reduction of DNA concentrations in Airway Secretions
Secondary	length of stay at the Intensive Care Unit
Secondary	length of stay at the hospital