Preventive Inhalation of Hypertonic Saline in Infants With Cystic Fibrosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Heidelberg University
Sponsor:
Collaborator:
German Center for Lung Research (DZL)
Information provided by (Responsible Party):
Marcus A. Mall, MD, University of Heidelberg
ClinicalTrials.gov Identifier:
NCT01619657
First received: June 12, 2012
Last updated: June 21, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to assess whether 6% hypertonic saline (HS) is a safe and effective preventive therapy in newborns and infants with cystic fibrosis (CF).


Condition Intervention Phase
Cystic Fibrosis Lung Disease
Drug: 6% Hypertonic Saline (HS), 4mL
Drug: 0.9% Isotonic Saline (IS), 4mL
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Randomized, Double-blind, Controlled Pilot Study on Safety of Hypertonic Saline as Preventive Inhalation Therapy in Newborns and Infants With Cystic Fibrosis

Resource links provided by NLM:


Further study details as provided by Heidelberg University:

Primary Outcome Measures:
  • Number of patients in both treatment groups with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: during the 52 week treatment period ] [ Designated as safety issue: Yes ]
    Safety of inhalation with HS and IS in newborns and infants with CF assessed by proportion of adverse events (AEs) and serious adverse events (SAEs)


Secondary Outcome Measures:
  • Rate of protocol-defined pulmonary exacerbations [ Time Frame: during the 52 week treatment period ] [ Designated as safety issue: Yes ]
    Rate of protocol-defined pulmonary exacerbations requiring treatment with oral, inhaled or intravenous antibiotics between subjects randomized to HS and IS

  • Time to first pulmonary exacerbation in both treatment groups [ Time Frame: during the 52 week treatment period ] [ Designated as safety issue: Yes ]
  • Proportion of children with morphological and/or functional changes due to CF lung disease at baseline and after 1 year of inhalation [ Time Frame: during the 52 week treatment period ] [ Designated as safety issue: No ]
    Proportion of children with morphological and/or functional changes due to CF lung disease at baseline and after 1 year of inhalation according to magnetic resonance imaging (MRI) chest score and chest x-ray (CXR) Chrispin-Norman score in both groups (HS vs. IS)

  • Extent and severity of bronchial dilatation [ Time Frame: during the 52 week treatment period ] [ Designated as safety issue: No ]
    Extent and severity of bronchial dilatation after MRI and CXR scores at baseline and after 1 year of inhalation in both groups

  • Proportion of children with impairments in lung function [ Time Frame: during the 52 week treatment period ] [ Designated as safety issue: No ]
    Proportion of children with impairments in lung function determined via multiple breath washout at baseline, after 3, 6, 9, and 12 months of inhalation in both groups

  • Severity of impairment in lung function test [ Time Frame: during the 52 week treatment period ] [ Designated as safety issue: No ]
    Severity of impairment in lung function test at baseline, after 3, 6, 9, and 12 months of inhalation in both groups

  • Health-related quality of life [ Time Frame: during the 52 week treatment period ] [ Designated as safety issue: No ]
    Health-related quality of life as assessed by scores from Cystic Fibrosis Questionnaire - Revised Parent Report (CFQ-R, German version), administered quarterly

  • Change in anthropometric and basic respiratory parameters [ Time Frame: during the 52 week treatment period ] [ Designated as safety issue: Yes ]
    Change in weight, height, body mass-index, weight-for-height, resting respiratory rate, and room air oxygen saturation

  • Proportion of patients with new isolation of CF pathogen [ Time Frame: during the 52 week treatment period ] [ Designated as safety issue: No ]
    Among participants from whom Pseudomonas aeruginosa or other CF pathogens were not isolated from respiratory cultures prior to enrolment, the proportion from whom these organisms are isolated from clinically collected respiratory cultures

  • Time to first isolation of a CF pathogen [ Time Frame: during the 52 week treatment period ] [ Designated as safety issue: No ]
    Time to acquisition of a CF pathogen is going to be compared between both treatment groups


Estimated Enrollment: 40
Study Start Date: June 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hypertonic Saline Drug: 6% Hypertonic Saline (HS), 4mL
Administered via inhalation twice daily for 52 weeks. The delivery system is a PARI LC SPRINT® Junior nebulizer with a baby bend, size-adapted PARI® Baby face mask size 0-3, connection tubing (2.2m) and a PARI JuniorBOY® SX compressor.
Other Name: MucoClear® 6%
Active Comparator: Isotonic Saline Drug: 0.9% Isotonic Saline (IS), 4mL
Administered via inhalation twice daily for 52 weeks. The delivery system is a PARI LC SPRINT® Junior nebulizer with a baby bend, size-adapted PARI® Baby face mask size 0-3, connection tubing (2.2m) and a PARI JuniorBOY® SX compressor.
Other Name: Normal Saline

Detailed Description:

Cystic fibrosis (CF) remains one of the most common lethal genetic diseases in Europe and North America. Despite a substantial increase in life expectancy over the past decades, many CF patients still die during young adulthood due to chronic progressive CF lung disease that is caused by defective fluid transport by airway epithelia causing dehydration of airway surfaces, which in turn leads to impaired mucociliary clearance, chronic airway mucus obstruction, inflammation and infection. Recent evidence from studies in a mouse model of CF lung disease suggest that preventive improvement of airway surface hydration may be an effective treatment of early and reversible mucus obstruction and inflammation, and thus delay or ameliorate progressive damage in lungs of CF patients. Hypertonic saline (HS) is an osmotic agent that improves airway surface hydration, and inhalation of 6% HS is already an established, safe, and effective maintenance therapy that improves mucociliary clearance and lung function, and reduces pulmonary exacerbations in older children (> 6 years) and adults with chronic CF lung disease and fixed lung damage. However, the effect of HS as a preventive therapy has not been studied, and no other therapies are available for preventive improvement of airway dehydration and mucociliary dysfunction in CF.

This investigator initiated clinical trial is a monocentric, randomized, double-blind, controlled pilot study on safety and efficacy of a preventive and early inhalation with HS in newborns and infants with CF who are diagnosed in the newborn period either by CF newborn screening (CF-NBS) or for another reason (e.g. meconium ileus) and are younger than 4 months of age at the time of enrolment. Participating patients will be randomized to 6% HS or 0.9% isotonic saline (IS) as active comparator. In both groups, patients will inhale their study solution twice daily over 52 weeks. At the beginning, during and at the end of the study, different measurements will be undertaken to determine effects of HS on safety, radiologic and/or functional alterations of the lung, number of exacerbations, time to first detection of a CF pathogen, and health-related quality of life. We expect that the results of this study will provide first evidence on the safety and efficacy of a preventive therapy that improves airway surface hydration and targets a CF basic defect and may thus delay and/or ameliorate chronic damage of the lungs of patients with CF.

  Eligibility

Ages Eligible for Study:   up to 4 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed diagnosis of CF established in neonatal period either via CF newborn screening (NBS) or because of symptoms typical for CF (e.g. meconium ileus), positive family history or positive prenatal screening and fulfilling at least one of the following three criteria:

    • sweat chloride ≥ 60mEq/L
    • two CF causing mutations of CFTR gen
    • alterations of transepithelial potential difference of nasal or rectal epithelia typical for CF.
  2. Age at enrolment is 0 to 4 months.
  3. Patient's and parent's ability to comply with medication use, study visits, and study procedures is judged by the investigator (therefore parents have to understand the character of the study and individual consequences).
  4. Participation in this study is voluntary. Only patients, whose parents or legal guardians gave written consent, are included.

Exclusion Criteria:

  1. Born < 30 weeks gestation.
  2. Prolonged mechanical ventilation in the first 3 months of life.
  3. A significant medical disease or condition other than CF likely to interfere with the child's ability to complete the entire protocol.
  4. Previous major surgery except for meconium ileus.
  5. Other major organ dysfunction, excluding pancreatic or hepatic dysfunction or another condition due to cystic fibrosis.
  6. Physical findings that would compromise the safety of the subject or the quality of the study data as determined by investigator.
  7. History of adverse reaction to sedation.
  8. Known hypersensitivity to study treatment.
  9. Participation in other interventional studies at the same time.

Criteria, which lead to a displacement of the procedures in sedation until the child has recovered:

  • Clinically significant upper airway obstruction as determined by investigator (e.g. severe laryngomalacia, markedly enlarged tonsils, significant snoring, diagnosed obstructive sleep apnoea).
  • Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset in 2 weeks preceding visit.
  • Oxygen saturation <95% before initial pulmonary function test or initial MRI.
  • Severe gastroesophageal reflux, defined as persistent frequent emesis despite anti-reflux therapy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01619657

Contacts
Contact: Marcus A Mall, MD +49 6221 56 4502 Marcus.Mall@med.uni-heidelberg.de
Contact: Mirjam Stahl, MD +49 6221 56 37049 Mirjam.Stahl@med.uni-heidelberg.de

Locations
Germany
University Children's Hospital Heidelberg, Cystic Fibrosis Centre Recruiting
Heidelberg, Baden-Württemberg, Germany, 69120
Contact: Marcus A Mall, MD    +49 6221 56 4502    Marcus.Mall@med.uni-heidelberg.de   
Contact: Mirjam Stahl, MD    +49 6221 56 37049    Mirjam.Stahl@med.uni-heidelberg.de   
Sub-Investigator: Olaf Sommerburg, MD         
Principal Investigator: Mirjam Stahl, MD         
Sub-Investigator: Susanne Hämmerling, MD         
Sub-Investigator: Eva Fritzsching, MD         
Principal Investigator: Marcus A Mall, MD         
University Hospital Gießen and Marburg GmbH Not yet recruiting
Gießen, Germany, 35392
Contact: Lutz Nährlich, MD    +49 (0) 641 985-57621    lutz.naehrlich@paediat.med.uni-giessen.de   
Principal Investigator: Lutz Nährlich, MD         
Medizinische Hochschule Hannover Not yet recruiting
Hannover, Germany, 30625
Contact: Christian Dopfer, MD    +49 (0)1761 532 3325    dopfer.christian@mh-hannover.de   
Principal Investigator: Christian Dopfer, MD         
University Children's Hospital Schleswig-Holstein Not yet recruiting
Lübeck, Germany, 23538
Contact: Matthias V Kopp, MD    +49 (0) 451 5002550    matthias.kopp@uksh.de   
Principal Investigator: Matthias V Kopp, MD         
Sponsors and Collaborators
Heidelberg University
German Center for Lung Research (DZL)
Investigators
Principal Investigator: Marcus A Mall, MD University Hospital Heidelberg
  More Information

No publications provided

Responsible Party: Marcus A. Mall, MD, Prof. Dr. med., University of Heidelberg
ClinicalTrials.gov Identifier: NCT01619657     History of Changes
Other Study ID Numbers: UKH-PIHSNC-1
Study First Received: June 12, 2012
Last Updated: June 21, 2013
Health Authority: Germany: Ethics Commission

Keywords provided by Heidelberg University:
Cystic Fibrosis
Hypertonic Saline
Infant
Newborn
Prevention

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Lung Diseases
Pulmonary Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 23, 2014