Dose-finding and safety of heparin aerosol application in idiopathic pulmonary fibrosis

ISRCTN	ISRCTN43849290
DOI	https://doi.org/10.1186/ISRCTN43849290
Protocol serial number	DOSEFIB 18-NOV-05
Sponsor	Individual Sponsor (Germany)
Funder	German Research Council (Deutsche Forschungsgemeinschaft) (DFG)

Submission date: 16/02/2006
Registration date: 28/04/2006
Last edited: 03/05/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Andreas Guenther
Scientific

Department of Internal Medicine
Klinikstr. 36
Giessen
35392
Germany

Phone	+49 (0)6 4142 502
Email	andreas.guenther@innere.med.uni-giessen.de

Study information

Primary study design	Interventional
Study design	Open label, single site
Secondary study design	Single-centre
Scientific title	Dose-finding and safety of heparin aerosol application in idiopathic pulmonary fibrosis
Study acronym	DOSEFIB
Study objectives	To identify suitable amounts of inhaled heparin that result in a prolonged alveolar anticoagulatory activity and to assess safety and tolerability of such heparin treatment in a period of 4 weeks
Ethics approval(s)	Approved by the Ethics Committee of the School of Medicine, Justus-Liebig-University Giessen, Germany on 21/02/2006, reference number: 11/06
Health condition(s) or problem(s) studied	Idiopathic Pulmonary Fibrosis
Intervention	Triple daily inhalation of 10,000 up to 24,000 units of unfractioned heparin
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Heparin
Primary outcome measure(s)	Safety as based on the following five safety events: 1. Any otherwise unexplainable decline in forced vital capacity by more than 10% 2. Any otherwise unexplainable decline in diffusion capacity by more than 10% 3. Any otherwise unexplainable decline in 6 min walking distance by more than 20% 4. Any otherwise unexplainable decline in serum hemoglobin by more than 10% 5. Any occurrence of hemoptysis
Key secondary outcome measure(s)	1. Frequency of heparin induced antibodies 2. Recalcification times of bronchoalveolar lavage (BAL) fluids obtained at end of study 3. Change in capillary oxygen partial pressure 4. Change in oxygen saturation
Completion date	01/08/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	20
Total final enrolment	19
Key inclusion criteria	1. Patients with idiopathic pulmonary fibrosis (IPF) according to consensus criteria 2. Age between 18 and 70 3. Completion of physical examination 4. Body weight of more than 40 kg 5. 40% < forced vital capacity (FVC) < 90% 6. 30% < diffusing capacity of the lung for carbon monoxide (Dlco) < 75% 7. Capillary pO2 >55 mmHg (with or without O2) 8. Signed informed consent 9. Requirements of Local Ethics Committee are met
Key exclusion criteria	1. Any hemoptysis of unknown reason 2. Any significant and otherwise unexplainable bleeding with reduction of hemoglobin values by more than 10% in patient’s history 3. Pre-existing presence of heparin induced antibodies 4. Preceding surgery within last 6 weeks 5. Current gastric or duodenal ulcer or inflammatory bowel disease 6. Any oesophageal varicosis of any size 7. Current colon adenoma with previous gastrointestinal bleeding 8. Current lower respiratory tract infection with CRP >10 mg/l 9. Any suspected or proven active malignancy, especially lung cancer 10. Any need for systemic anticoagulation with International Normalized Ratio (INR) >1.5 11. Any treatment with another investigational drug 12. Acute or chronic left heart failure 13. Severe arterial hypertension (>200 mmHg systolic or >120 mmHg diastolic) 14. Inherited or acquired coagulation disorders resulting in prolonged bleeding time or an INR >1.5 15. Disseminated intravascular coagulation 16. Deficient thrombocyte function or platelet counts <40,000 /µl 17. Evidence for intracranial hemorrhage 18. Diabetic retinopathy 19. Severe hepatic insufficiency (bilirubin >10 mg%) 20. Renal insufficiency with creatinine values >3mg% or proteinuria >1 g per day 21. Primary or secondary immunodeficiency 22. Previous therapeutic radiation of the lungs or the mediastinum 23. Elevated intracranial pressure 24. Pregnancy, breast feading or lack of safe contraception 25. Patients whose underlying disease is not likely to permit them to survive the study - any hemoptysis of unknown reason 26. Sickle cell anemia
Date of first enrolment	01/03/2006
Date of final enrolment	01/08/2006

Locations

Countries of recruitment

Germany

Study participating centre

Department of Internal Medicine

Giessen
35392
Germany

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/06/2010	03/05/2019	Yes	No

Editorial Notes

03/05/2019: Publication reference and total final enrolment added.