Effect of Intravenous Administration of C1-inhibitor on Inflammation and Coagulation After Bronchial Instillation of House Dust Mite Allergen and Lipopolysaccharide in Allergic Asthma Patients
| Registry | NCT03051698, acronym CAST |
|---|---|
| Status | Terminated - Interim analysis showed no differences between groups |
| Phase | Phase 4 |
| Study type | Interventional; randomized, parallel, masking: double, treatment |
| Enrollment | 37 (Actual) |
| Sponsor | T. van der Poll (Other); collaborators: ZonMw: The Netherlands Organisation for Health Research and Development, Prothya Biosolutions |
| Conditions | Asthma |
| Interventions | C1-inhibitor, Saline, Antibiotics (Drug, other) |
| Dates | start 2016-11-16, primary completion 2019-10-23, completion 2019-10-23, first posted 2017-02-14, last updated 2020-06-24 |
| Locations | 1 site in Netherlands |
Related Papers Related Patents Related Grants Related Experts
All trials for Asthma All trials of C1-inhibitor All trials of Saline
The purpose of this proof-of-concept study is to determine the effect of Intestinal Microbiota Depletion or Intravenous Administration of C1-inhibitor on Inflammation and Coagulation after Bronchial Instillation of House Dust Mite Allergen and Lipopolysaccharide in Allergic Asthma Patients
Intravenous administration of C1-inhibitor (n=20) or vehicle (n=20). One group of patients (n=20) will receive broad spectrum antibiotics (vancomycin, ciprofloxacin, metronidazole) for 7 days (washout 36 hours before study day). This group will receive the same vehicle as the control group 2 hours prior to challenge. HDM will be administered together with the environmental pollutant LPS in a lung subsegment via a bronchoscope (mimicking environmental exposure to HDM); a contralateral lung subsegment will be administered with saline (control side). After 7 hours, bronchoalveolar lavage (BAL) fluid will be harvested by a second bronchoscopy. Blood samples will be collected before administration of C1-inhibitor or vehicle, and before both bronchoscopies. Faeces will be collected prior to antibiotic administration as well as prior to HDM+LPS challenge.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| C1-inhibitor | Experimental | Drug: C1-inhibitor | One gift of intravenous administration of C1-inhibitor (Cinryze, 100U/kg) during one hour |
| Saline | Placebo comparator | Other: Saline | One gift of intravenous administration of 0.9% NaCl during one hour. |
| Antibiotics | Experimental | Drug: Antibiotics | broad spectrum antibiotics (vancomycin, ciprofloxacin, metronidazole) for 7 days (washout 36 hours before study day). |
Sex: All, ages: 18 Years to 45 Years
Inclusion Criteria: * Intermittent to mild asthma according to the Global Initiative for Asthma (GINA) criteria * Allergy for HDM documented by a positive RAST and a positive skin prick test. * No clinically significant findings during physical examination and hematological and biochemical screening * At spirometry FEV1 more than 70% of predicted value * A PC20 between 0.3 - 9.6 mg/ml (corresponding with increased airway hyperreactivity) * Able to communicate well with the investigator and to comply with the requirements of the study * Stable asthma without the use of asthma medication 2 weeks prior to the study day. As documented by the Juniper's Asthma control questionnaire (ACQ) score < 1,2. * Written informed consent * No current smoking for at least 1 year and less than 10 pack years of smoking history Exclusion Criteria: * Relevant comorbidity, pregnancy and/or recent surgical procedures. * A history of smoking within the last 12 months, or regular consumption of greater than three units of alcohol per day * Exacerbation and/ or the use of asthma medication within 2 weeks before start * Administration of any investigational drug within 30 days of study initiation * Donation of blood within 60 days, or loss of greater than 400 ml of blood within 12 weeks of study initiation\] * History of venous or arterial thromboembolic disease * History of enhanced bleeding tendency or abnormal clotting test results. * History of serious drug-related reactions, including hypersensitivity * Inability to maintain stable without the use of asthma medication 2 weeks before start of the study
| Facility | City | Country | Status |
|---|---|---|---|
| Academic Medical Center | Amsterdam, North Holland | Netherlands |