Time of Ventilation and Lung Function of Ventilated Patients Under Therapy With Dornase Alfa - Full Text View

Purpose

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

Condition	Intervention	Phase
Long Term Ventilation	Drug: dornase alfa	Phase 2 Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Prevention
Official Title:	Beatmungsdauer Und Lungenfunktion Bei Beatmeten Patienten Unter Therapie Mit Dornase Alfa - Randomisierte, Doppel-Blinde, Placebo-Kontrollierte, Multizentrische, Prospektive Klinische Studie

Resource links provided by NLM:

Drug Information available for: Dornase alfa

U.S. FDA Resources

Further study details as provided by University Hospital Tuebingen:

Primary Outcome Measures:

Time of mechanical ventilation from beginning of the ventilation-therapy up to the end of the ventilation-therapy

Secondary Outcome Measures:

reduction of atelectasis / dystelectasis
improval of pulmonaryfunction
reduction of pneumonia
reduction of DNA concentrations in Airway Secretions
length of stay at the Intensive Care Unit
length of stay at the hospital

Estimated Enrollment:	540
Study Start Date:	August 2003
Estimated Study Completion Date:	July 2006

Detailed 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).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00204685

Locations

Germany
University Hospital, Anaesthesiology
Tuebingen, Baden-Wuerttemberg, Germany, 72076
Universität Charité, Campus Mitte, Anästhesie, Intensivstation
Berlin, Germany, 10117
Charité, Universitätsmedizin Berlin, Campus Mitte, Innere Intensivstation
Berlin, Germany, 10117
Vivantes Klinikum Spandau, Klinik für Anästhesie
Berlin, Germany, 13585
Klinikum Chemnitz gGmbH, Innere Medizin
Chemnitz, Germany, 09113
Universitätsklinikum Erlangen Medizinische Klinik, Intensivstation I
Erlangen, Germany, 91054
Universitätsklinikum, Innere Medizin, Intensivstation
Frankfurt, Germany, 60590
Universitätsklinikum Hamburg-Eppendorf, Medizinische Intensivstation
Hamburg, Germany, 20246
Medizinische Hochschule Hannover, Anästhesiologie
Hannover, Germany, 30625
Anästhesiolog. Klinik der Ruprecht-Karls-Universität
Heidelberg, Germany, 69120
Universitätsklinikum des Saarlandes, Innere Medizin III, Internistische Intensivstation
Homburg / Saar, Germany, 66421
Klinik für Anästhesiologie u. IntensivtherapieUniversität Leipzig
Leipzig, Germany, 04103
Department of internal Medicine
Luedenscheid, Germany, 58505
Universitätsklinik Lübeck, Medizinische Klinik 1
Lübeck, Germany, 23538
Universität Magdeburg, Innere Medizin,
Magdeburg, Germany, 39120
Johannes-Gutenberg-Universität, Neurochirurgische Klinik
Mainz, Germany, 55131
Gutenberg-Universität, Anästhesie-Intensivstation
Mainz, Germany, 55131
Johannes Gutenberg-Universität Mainz, II. Medizinische Klinik, Intensivstation
Mainz, Germany, 55131
Universitätsklinikum Mannheim, I. Med. Klinik
Mannheim, Germany, 68167
Klinikum der Philipps-Universität Marburg, Intensivstation III
Marburg, Germany, 35033
Ludwig Maximilians Universität München, Großhadern, Neurologie-Intensiv
München, Germany, 81377
Klinikum der Univ. München Großhadern, Anaesthesiologische Intensivstation
München, Germany, 81377
Klinikum der Univ. München Großhadern
München, Germany, 81377
Berufsgenossenschaftliche Klinik Tuebingen, Intensive care Unit
Tuebingen, Germany, 72076
Intensive Care Unit of the Internal Department, Universitiy of Tuebingen
Tuebingen, Germany, 72076

Sponsors and Collaborators

University Hospital Tuebingen

Joachim Riethmueller, Dr. med.

Investigators

Study Director:

Joachim Riethmueller, Dr. med.

University Children’s Hospital Tuebingen

More Information

Publications:

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.

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.

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.

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.

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.

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.

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.

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.

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.

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. No abstract available.

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.

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.

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

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

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. No abstract available.

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.

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.

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.

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.

Brandt T, Breitenstein S, von der Hardt H, Tummler 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.

Grassme H, Kirschnek S, Riethmueller J, Riehle A, von Kurthy 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.

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

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.

ClinicalTrials.gov Identifier:	NCT00204685 History of Changes
Other Study ID Numbers:	LUFIT
Study First Received:	September 9, 2005
Last Updated:	September 13, 2006
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

ClinicalTrials.gov processed this record on May 22, 2013