Cystic FibrosisISISNCT00709280
Infant Study of Inhaled Saline in Cystic Fibrosis
A study testing 7% Hypertonic Saline (HS) and 0.9% Isotonic Saline (IS) in people with Cystic Fibrosis, run by CF Therapeutics Development Network Coordinating Center at 30 sites in 2 countries.
Trial summary
The purpose of this study is to assess whether 7% hypertonic saline (HS) is an effective and safe therapy in infants and young children with CF. Read more about this study
- Who is it for?
- Ages 4 to 59 months
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- 7% Hypertonic Saline (HS) and 0.9% Isotonic Saline (IS)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 321 participants
- Where
- 30 sitesin 2 countries
- Study dates
- Apr 2009to Nov 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 59 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Diagnosis of CF by newborn screening or at least one clinical feature of CF, AND either: (a) A documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis or (b) A genotype with two identifiable CF-causing mutations
- Informed consent by parent or legal guardian
- Age 4 months to < 60 months at Enrollment visit. If participating in Infant Pulmonary Function testing (selected sites), age 4 months to < 16 months at Enrollment visit.
- Ability to comply with medication use, study visits, and study procedures as judged by the site investigator
Who cannot join
- Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset in 1 week preceding Enrollment visit
- Acute wheezing at Enrollment visit (prior to HS test dose), or at Infant PFT visit (prior to infant pulmonary function testing), as applicable
- Oxygen saturation < 95% (< 90% in centers located above 4000 feet elevation) at Enrollment visit (prior to HS test dose) or at Infant PFT visit (prior to infant pulmonary function testing), as applicable
- Other major organ dysfunction, excluding pancreatic dysfunction
- Physical findings that would compromise the safety of the subject or the quality of the study data as determined by the site investigator
- Investigational drug use within 30 days prior to Enrollment visit, or within 30 days prior to Infant PFT visit as applicable
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- Treatment with inhaled hypertonic saline at any concentration within 30 days of Enrollment visit, or within 30 days prior to Infant PFT visit as applicable
- Chronic lung disease not related to CF
- Intolerance of test dose of HS at Enrollment visit
- A sibling that has been randomized and is still enrolled in ISIS002
- Additional Exclusion Criteria for Participation in Infant Pulmonary Function Testing:
- History of adverse reaction to sedation
- Clinically significant upper airway obstruction as determined by the Site Investigator (e.g. severe laryngomalacia, markedly enlarged tonsils, significant snoring, diagnosed obstructive sleep apnea)
- Severe gastroesophageal reflux, defined as persistent frequent emesis despite anti-reflux therapy
- Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset in 2 weeks preceding visit
Trial locations and contacts
30 sites in 2 countries.
30 sites in 2 countries
United States28 sites
University of Michigan / C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109
The Children's Hospital
Aurora, Colorado, 80045
Johns Hopkins University / Johns Hopkins Hospital
Baltimore, Maryland, 21287
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Women and Children's Hospital of Buffalo
Buffalo, New York, 14222
University of North Carolina
Chapel Hill, North Carolina, 27599
University of Virginia - Pediatric Respiratory Medicine
Charlottesville, Virginia, 22908
Children's Memorial Hospital and Northwestern University
Chicago, Illinois, 60614
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Nationwide Children's Hospital, Pulmonary Division
Columbus, Ohio, 43205
Texas Children's Hospital
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
University of Louisville
Louisville, Kentucky, 40202
University of Wisconsin
Madison, Wisconsin, 53792
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, 55404
University of Nebraska
Omaha, Nebraska, 68198
Stanford University / Lucile S. Packard Children's Hospital
Palo Alto, California, 94304
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15201
University of Rochester Medical Center
Rochester, New York, 14642
University of Utah
Salt Lake City, Utah, 84108
Children's Hospital & Regional Medical Center
Seattle, Washington, 98105
Cardinal Glennon Children's Hospital
St Louis, Missouri, 63104
Washington University in St. Louis
St Louis, Missouri, 63110
SUNY Upstate Medical University
Syracuse, New York, 13210
Canada2 sites
Hospital For Sick Children
Toronto, Ontario, M5G 1X8
BC Children's Hospital
Vancouver, British Columbia, V6H 3V4
About this study
The purpose of this study is to assess whether 7% hypertonic saline (HS) is an effective and safe therapy in infants and young children with CF.
Read the detailed description
A growing body of evidence supports the importance of intervention in Cystic Fibrosis (CF) lung disease during infancy and early childhood, in order to potentially delay or prevent irreversible lung disease. Yet, aside from antimicrobial therapies, the CF community has no clinical trial evidence base with which to guide pulmonary therapies in children <6 years of age. Hypertonic Saline (HS) is the most attractive chronic maintenance therapy to investigate in these young children because it addresses defective mucociliary clearance, an early step in the cascade of events leading to CF lung disease that is expected to be abnormal prior to the onset of airway infection and inflammation.
This study is a randomized, parallel group, controlled trial to assess the efficacy and safety of 7% HS inhaled twice daily for 48 weeks among young children with CF 4 to < 60 months of age at enrollment. The primary hypothesis is that, compared to isotonic saline (IS), HS will decrease the number of protocol-defined pulmonary exacerbations during the 48 week treatment period. The results of the proposed trial may for the first time provide evidence for early initiation of HS, which, by improving mucociliary clearance, may delay or hinder the cycle of infection and inflammation responsible for progressive airway damage in CF lung disease.
- Conditions
- Cystic Fibrosis
- Being tested
- 7% Hypertonic Saline (HS), 0.9% Isotonic Saline (IS)
- Keywords
- Cystic Fibrosis, hypertonic saline, inhaled saline
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
7% Hypertonic Saline (HS)Drug
Also called Hyper-Sal™, inhaled saline
Administered via inhalation twice daily for 48 ± 4 weeks. The delivery system is a PARI Sprint Junior nebulizer with a PARI Baby face mask or mouthpiece driven by a PARI Pro Neb compressor.
0.9% Isotonic Saline (IS)Drug
Also called Normal saline
Administered via inhalation twice daily for 48 ± 4 weeks. The delivery system is a PARI Sprint Junior nebulizer with a PARI Baby face mask or mouthpiece driven by a PARI Pro Neb compressor.
| Study group | Role | What they receive |
|---|---|---|
| Active treatment group | Experimental | 7% Hypertonic Saline administered via inhalation twice daily for 48 ± 4 weeks Receives: Drug: 7% Hypertonic Saline (HS) |
| Control group | Active comparator | 0.9% Isotonic Saline administered via inhalation twice daily for 48 ± 4 weeks Receives: Drug: 0.9% Isotonic Saline (IS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The rate of protocol-defined pulmonary exacerbations requiring treatment with oral, inhaled or intravenous antibiotics between subjects randomized to HS and IS
Measured: during the 48 week treatment period
Secondary outcomes (6)
Symptoms by parent home questionnaire administered weekly
Measured: during the 48 week treatment period
Health-related quality of life as assessed by scores from Cystic Fibrosis Questionnaire-Revised Parent Report (CFQ-R), administered quarterly
Measured: over the 48 week treatment period
Standardized cough score assessed at study visits
Measured: during the 48 week treatment period
Change in weight, height, resting respiratory rate, and room air oxygen saturation
Measured: over the 48 week treatment period
Among participants from whom Pseudomonas aeruginosa (Pa) and other CF pathogens were not isolated from respiratory cultures prior to enrollment, the proportion from whom these organisms are isolated from clinically collected respiratory cultures
Measured: measured at baseline and at 48 weeks
Pulmonary function indices measured at baseline and 48 weeks in infants 4 to 15 months of age at enrollment participating in infant pulmonary function testing (N = 100, selected sites)
Measured: over the 48 week treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2008 (estimated)
- Study startApr 2009
- Primary completionOct 2011
- Study completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 321 participants (actual)
Sponsor and investigators
- Lead sponsor
- CF Therapeutics Development Network Coordinating Center
- Sponsor type
- Research network
- Collaborators
- Cystic Fibrosis Foundation, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Stephanie Davis, MD, Principal investigator, University of North Carolina, Chapel HillMargaret Rosenfeld, MD, MPH, Principal investigator, Children's Hospital and Regional Medical CenterFelix Ratjen, MD, PhD, Principal investigator, University of Toronto Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00709280
- Sponsor's protocol ID
- ISIS002
- Other IDs
- U01HL092931, U01HL092932
- Acronym
- ISIS
- Status last verified
- Feb 2013
- First submitted
- 1 Jul 2008
- Last updated
- 12 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rosenfeld M, Ratjen F, Brumback L, Daniel S, Rowbotham R, McNamara S, Johnson R, Kronmal R, Davis SD; ISIS Study Group. Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial. JAMA. 2012 Jun 6;307(21):2269-77. doi: 10.1001/jama.2012.5214.
PubMed 22610452Subbarao P, Stanojevic S, Brown M, Jensen R, Rosenfeld M, Davis S, Brumback L, Gustafsson P, Ratjen F. Lung clearance index as an outcome measure for clinical trials in young children with cystic fibrosis. A pilot study using inhaled hypertonic saline. Am J Respir Crit Care Med. 2013 Aug 15;188(4):456-60. doi: 10.1164/rccm.201302-0219OC.
PubMed 23742699
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Infant Study of Inhaled Saline in Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT00709280
- Acronym / sponsor ID
- ISIS / ISIS002
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic Fibrosis, hypertonic saline, inhaled saline
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 321 participants (actual)
- Lead sponsor
- CF Therapeutics Development Network Coordinating CenterResearch network
- Collaborators
- Cystic Fibrosis Foundation, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Apr 2009
- Primary completion
- Oct 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 3 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess whether 7% hypertonic saline (HS) is an effective and safe therapy in infants and young children with CF.
Detailed description
A growing body of evidence supports the importance of intervention in Cystic Fibrosis (CF) lung disease during infancy and early childhood, in order to potentially delay or prevent irreversible lung disease. Yet, aside from antimicrobial therapies, the CF community has no clinical trial evidence base with which to guide pulmonary therapies in children <6 years of age. Hypertonic Saline (HS) is the most attractive chronic maintenance therapy to investigate in these young children because it addresses defective mucociliary clearance, an early step in the cascade of events leading to CF lung disease that is expected to be abnormal prior to the onset of airway infection and inflammation.
This study is a randomized, parallel group, controlled trial to assess the efficacy and safety of 7% HS inhaled twice daily for 48 weeks among young children with CF 4 to < 60 months of age at enrollment. The primary hypothesis is that, compared to isotonic saline (IS), HS will decrease the number of protocol-defined pulmonary exacerbations during the 48 week treatment period. The results of the proposed trial may for the first time provide evidence for early initiation of HS, which, by improving mucociliary clearance, may delay or hinder the cycle of infection and inflammation responsible for progressive airway damage in CF lung disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active treatment group | Experimental | Drug: 7% Hypertonic Saline (HS)7% Hypertonic Saline administered via inhalation twice daily for 48 ± 4 weeks |
| Control group | Active comparator | Drug: 0.9% Isotonic Saline (IS)0.9% Isotonic Saline administered via inhalation twice daily for 48 ± 4 weeks |
Who may qualify
- Ages
- 4 to 59 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Diagnosis of CF by newborn screening or at least one clinical feature of CF, AND either: (a) A documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis or (b) A genotype with two identifiable CF-causing mutations
- Informed consent by parent or legal guardian
- Age 4 months to < 60 months at Enrollment visit. If participating in Infant Pulmonary Function testing (selected sites), age 4 months to < 16 months at Enrollment visit.
- Ability to comply with medication use, study visits, and study procedures as judged by the site investigator
Key exclusion criteria (15 listed)
- Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset in 1 week preceding Enrollment visit
- Acute wheezing at Enrollment visit (prior to HS test dose), or at Infant PFT visit (prior to infant pulmonary function testing), as applicable
- Oxygen saturation < 95% (< 90% in centers located above 4000 feet elevation) at Enrollment visit (prior to HS test dose) or at Infant PFT visit (prior to infant pulmonary function testing), as applicable
- Other major organ dysfunction, excluding pancreatic dysfunction
- Physical findings that would compromise the safety of the subject or the quality of the study data as determined by the site investigator
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 7% Hypertonic Saline (HS)Also: Hyper-Sal™, inhaled salineAdministered via inhalation twice daily for 48 ± 4 weeks. The delivery system is a PARI Sprint Junior nebulizer with a PARI Baby face mask or mouthpiece driven by a PARI Pro Neb compressor. | Drug | Active treatment group |
| 0.9% Isotonic Saline (IS)Also: Normal salineAdministered via inhalation twice daily for 48 ± 4 weeks. The delivery system is a PARI Sprint Junior nebulizer with a PARI Baby face mask or mouthpiece driven by a PARI Pro Neb compressor. | Drug | Control group |
Primary outcome
The rate of protocol-defined pulmonary exacerbations requiring treatment with oral, inhaled or intravenous antibiotics between subjects randomized to HS and IS
Time frame: during the 48 week treatment period
6 secondary outcomes
Symptoms by parent home questionnaire administered weekly
Time frame: during the 48 week treatment period
Health-related quality of life as assessed by scores from Cystic Fibrosis Questionnaire-Revised Parent Report (CFQ-R), administered quarterly
Time frame: over the 48 week treatment period
Standardized cough score assessed at study visits
Time frame: during the 48 week treatment period
Change in weight, height, resting respiratory rate, and room air oxygen saturation
Time frame: over the 48 week treatment period
Among participants from whom Pseudomonas aeruginosa (Pa) and other CF pathogens were not isolated from respiratory cultures prior to enrollment, the proportion from whom these organisms are isolated from clinically collected respiratory cultures
Time frame: measured at baseline and at 48 weeks
Pulmonary function indices measured at baseline and 48 weeks in infants 4 to 15 months of age at enrollment participating in infant pulmonary function testing (N = 100, selected sites)
Time frame: over the 48 week treatment period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2013.
- Results publication: PubMed 22610452Rosenfeld M, Ratjen F, Brumback L, Daniel S, Rowbotham R, McNamara S, Johnson R, Kronmal R, Davis SD; ISIS Study Group. Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial. JAMA. 2012 Jun 6;307(21):2269-77. doi: 10.1001/jama.2012.5214.
- Derived from this study: PubMed 23742699Subbarao P, Stanojevic S, Brown M, Jensen R, Rosenfeld M, Davis S, Brumback L, Gustafsson P, Ratjen F. Lung clearance index as an outcome measure for clinical trials in young children with cystic fibrosis. A pilot study using inhaled hypertonic saline. Am J Respir Crit Care Med. 2013 Aug 15;188(4):456-60. doi: 10.1164/rccm.201302-0219OC.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephanie Davis, MD principal investigator
University of North Carolina, Chapel Hill
Margaret Rosenfeld, MD, MPH principal investigator
Children's Hospital and Regional Medical Center
Felix Ratjen, MD, PhD principal investigator
University of Toronto Hospital for Sick Children
30 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 7% Hypertonic Saline (HS) and 0.9% Isotonic Saline (IS) in people with Cystic Fibrosis, run by CF Therapeutics Development Network Coordinating Center at 30 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The rate of protocol-defined pulmonary exacerbations requiring treatment with oral, inhaled or intravenous antibiotics between subjects randomized to HS and IS (time frame: during the 48 week treatment period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00709280, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2013.