Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Double-blind, Controlled Pilot Study on Safety of Hypertonic Saline as Preventive Inhalation Therapy in Newborns and Infants With Cystic Fibrosis
Brief Summary: 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).


Options:
A: Inclusion Criteria:

* Gender: Females or Males. If the subject is female and of childbearing potential (first menses has occurred), she must have a documented negative pregnancy test at screening and prior to each mucociliary clearance study. Those of childbearing potential must be abstinent or using an acceptable method of birth control (i.e. an Intrauterine Contraceptive Device with a failure rate of \<1%, hormonal contraceptives or a barrier method).
* Age: 5-12 years, inclusive
* Diagnosis: Cystic fibrosis documented by a compatible clinical presentation and sweat chloride \> 60 mEq/l or 2 disease causing CFTR mutations.
* Severity of the Disease: Suitable patients will have mild lung disease, as defined by:

  * Pulmonary Function: Each patient must have an FEV1 of greater than or equal to 60% of predicted at the screening visit.
  * Hemoglobin saturation: Patients must have an oxygen saturation of \>92% on room air as determined by pulse oximetry at the screening visit.
* Informed consent - The patient and a parent or legally authorized guardian must agree to the subject's participation in the study by signing and dating the informed consent/assent forms after the nature of the study has been fully explained and all questions have been satisfactorily answered.

Exclusion Criteria:

* Unstable or asthmatic lung disease: As defined by a change in medical regimen during the preceding 2 weeks; an FEV1 15% below recent (within 6 months) clinical measurements. Patients with a history of co-existent asthma, as manifested by wheezing and significant bronchoreactivity (\>15% increase in FEV1 with bronchodilator), will also be excluded.
* Other medication usage: Patients unable or unwilling to be withdrawn from hypertonic saline therapy for two weeks prior to Visit 1 (baseline MCC visit). Patients using Pulmozyme will be permitted to participate in this trial. Patients on chronic, cycling antibiotics will be required to have completed at least 2 full cycles of the prescribed antibiotic prior to enrollment and should not cycle on or off this therapy during the treatment period of the study.
* Spirometry Performance: Those subjects who are unable to perform acceptable, reproducible spirometry will be excluded from this study.
* Drug allergy: A history of allergy or intolerance to any of the study medications, including albuterol or hypertonic saline.
* Have received an investigational drug or therapy during the preceding 30 days.
* Have had radiation exposure within the past year that would cause them to exceed Federal Regulations by participating in this study.
B: Inclusion Criteria:

* Male and female patients, \>/= 6 years of age
* Confirmed diagnosis of cystic fibrosis (CF)
* Receiving Pulmozyme once daily chronically for treatment of CF for at least 6 months prior to screening
* Percent predicted FEV1 \>/= 40% at screening based on the Wang (males \< 18 years, females \< 16 years) or Hankinson (males \>/= 18 years, females \>/= 16 years) standardized equations
* Able to reproducibly perform spirometry testing and comply with study assessments

Exclusion Criteria:

* An acute respiratory infection or pulmonary exacerbation within 4 weeks prior to randomization
* Initiation of any new chronic therapy (e.g. inhaled corticosteroids, inhaled oral antibiotics, high-dose ibuprofen, hypertonic saline, ivacaftor) for respiratory disease within 4 weeks prior to randomization
* Changes in chest physiotherapy schedule within 4 weeks prior to randomization
* Hospitalization within 4 weeks prior to randomization
* Planned hospitalization during the 6-week study
* History of organ transplantation
* Participation in an investigational drug or device study within 30 day prior to screening
C: 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.
D: Inclusion Criteria:

* Subjects with CF (medical record evidence of CFTR(Cystic fibrosis transmembrane conductance regulator) mutation or sweat chloride test or nasal voltage difference, and 1 or more clinical findings of CF),
* Age 12 or greater
* FEV1 \> 30% predicted(within the last 14 days and oxygen saturation \> 90% on FiO2(fraction of inspired oxygen) ≤ 50%,
* Admitted for an exacerbation,
* Use of effective contraception in women,
* Able to provide written informed consent.

Exclusion Criteria:

* Pregnancy,
* History of asthma based on methacholine challenge or bronchial hyperresponsiveness on PFTS(Pulmonary Function Test),
* Hemoptysis more than 60 mL within the last 30 days,
* Use of any investigational study drug within the last 30 days,
* Initiation of hypertonic saline within the last 30 days,
* A serum creatinine 2 mg/dl or more
* Active malignancy in the last year
* Antibiotics for CF exacerbation as an outpatient in the last 2 weeks
* B cepacia colonization
* Waiting list for lung transplant
* Lack of FEV1 data from the last 14 days
* Previous participation in this study

Answer: C