Respiratory FailurePhase 1/2NCT01945944
Nebulized Hypertonic Saline for Mechanically Ventilated Children
A Phase 1/2 study testing Hypertonic saline (3%) in people with Respiratory Failure, run by University Hospitals Cleveland Medical Center at 1 site in United States.
Trial summary
Children who need to be on a ventilator often have thick secretions/mucus in their lungs. These secretions can obstruct the breathing tube and their windpipe, which can worsen lung function and prolong the need for the ventilator. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Respiratory Failure
- What is being tested?
- Hypertonic saline (3%)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to May 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- invasive mechanical ventilation of < 12 hrs duration prior to enrollment
- expected duration of mechanical ventilation of > 48hrs from enrollment
- age < 18yo
- cystic fibrosis
- status asthmaticus
- pulmonary hemorrhage/contusion
Show all 11Show fewer
- home O2 use
- home non-invasive positive pressure (CPAP/BiPAP) ventilation use
- pre-existing tracheostomy
- prescription of mucolytic medication by primary clinical team
- allergy to inhaled saline/hypertonic saline or albuterol
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Rainbow Babies and Children's Hospital (of Univ. Hospitals Case Med. Center)
Cleveland, Ohio, 44106
About this study
Children who need to be on a ventilator often have thick secretions/mucus in their lungs. These secretions can obstruct the breathing tube and their windpipe, which can worsen lung function and prolong the need for the ventilator. Hypertonic saline is a medicine that is used to thin out secretions in patients with cystic fibrosis (and other conditions). We hypothesize that having children on a ventilator inhale this medication will shorten the amount of time that they need to be on the ventilator.
Read the detailed description
Recent pediatric data shows that less than 80% of children mechanically ventilated for ≥ 96 hours survived to PICU discharge, while 100% of children mechanically ventilated for < 96 hours survived to PICU discharge. Interventions that decrease duration of mechanical ventilation may improve outcome by limiting ventilator-induced lung injury, sedative medication usage and ventilator-associated pneumonia. Obstructive airway secretions may prolong mechanical ventilation by causing atelectasis and endotracheal tube obstruction, with resultant cardio-respiratory instability. Nebulized hypertonic saline (HTS) is used to decrease mucus viscosity and increase mucociliary clearance in patients with diseases such as cystic fibrosis and bronchiolitis, and has been used to enhance airway clearance in mechanically ventilated children. Administering nebulized HTS to mechanically ventilated children may facilitate airway clearance and shorten mechanical ventilation.
In a randomized study of children < 2 years old following cardiac surgery, patients given dornase, another mucolytic agent, had a significantly decreased duration of mechanical ventilation versus those given saline placebo (52 hrs vs. 82 hrs). HTS may be even more effective, as mechanically ventilated newborns with persistent atelectasis had more improvement in radiographic findings and oxygen saturation when randomized to receive hypertonic saline compared to those randomized to receive dornase. This may be because dornase may only be effective in patients with leukocytes or bacterial present in tracheal aspirates, while HTS may be effective in all ventilated patients. Further study of the impact of prophylactic mucolytic therapy on the duration of mechanical ventilation in children is warranted.
- Conditions
- Respiratory Failure
- Being tested
- Hypertonic saline (3%), Placebo (0.9% saline)
- Keywords
- pediatric, mucolytic, respiratory failure, atelectasis, hypertonic saline
- Medical subject headings
- Respiratory Insufficiency, Pulmonary Atelectasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypertonic saline (3%)Drug
Also called 3% saline
3mL of HTS given via nebulizer every 6hrs
Placebo (0.9% saline)Drug
Also called normal saline
3mL of normal saline given via nebulizer every 6hrs
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo (0.9% saline), 3mL every 6 hrs for up to 7 days Receives: Drug: Placebo (0.9% saline) |
| Hypertonic Saline | Experimental | Hypertonic saline (3%), 3mL every 6hrs for up to 7 days Receives: Drug: Hypertonic saline (3%) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of Mechanical Ventilation
Measured: typically 4 days - 2 weeks
Secondary outcomes (8)
Atelectasis
using chest x ray score. The score measures the amount of lung collapse ("atelectasis") observed on a chest x-ray. For each of the 5 lung lobes, 1 point is given for linear atelectasis, 2 points for sub-segmental atelectasis and 3 points for lobar atelectasis. The range is 0-15 points, with higher scores reflecting more severe lung collapse.
Measured: during mechanical ventilation (typically 4 days - 2 weeks)
Wheezing
as dichotomous outcome (yes/no) following drug administration
Measured: during mechanical ventilation (typically 4 days - 2 weeks)
ICU Length of Stay
Measured: during hospitalization (typically 4 days - 2 weeks)
Hospital Length of Stay
Measured: during hospitalization (typically 4 days - 2 weeks)
Change in Serum Sodium From Baseline
The baseline sodium was the last level measured prior to study initiation, typically within 24hrs of study initiation. The change in blood sodium level was calculated as the difference between the mean post-enrollment sodium level during ICU care and the sodium level at enrollment.
Measured: during hospitalization (typically 4 days - 2 weeks)
Dynamic Compliance
measured in ml/cm H20/kg using parameters on mechanical ventilator
Measured: during mechanical ventilation (typically 4 days - 2 weeks)
Oxygenation
SaO2/FiO2. This is a measure of how will the lungs are providing oxygen to the body. Higher ratios reflect better lung function.
Measured: during mechanical ventilation (typically 4 days - 2 weeks)
Dead Space
in % of tidal volume, using parameters on mechanical ventilator. Dead space is a measure of how much of the lung is not able to move air into and out of the body. Higher levels of dead space reflect higher levels of lung dysfunction.
Measured: during mechanical ventilation (typically 4 days - 2 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2013 (estimated)
- Study startOct 2013
- Primary completionApr 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Respiratory FailureStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals Cleveland Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Steven Shein, University Hospitals Cleveland Medical Center
- Investigators
- Steven L Shein, MD, Principal investigator, University Hospitals Cleveland Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01945944
- Sponsor's protocol ID
- 08-13-11
- Status last verified
- May 2016
- First submitted
- 12 Sep 2013
- Last updated
- 28 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Payen V, Jouvet P, Lacroix J, Ducruet T, Gauvin F. Risk factors associated with increased length of mechanical ventilation in children. Pediatr Crit Care Med. 2012 Mar;13(2):152-7. doi: 10.1097/PCC.0b013e3182257a24.
PubMed 21760567Riethmueller J, Borth-Bruhns T, Kumpf M, Vonthein R, Wiskirchen J, Stern M, Hofbeck M, Baden W. Recombinant human deoxyribonuclease shortens ventilation time in young, mechanically ventilated children. Pediatr Pulmonol. 2006 Jan;41(1):61-6. doi: 10.1002/ppul.20298.
PubMed 16265663Dilmen U, Karagol BS, Oguz SS. Nebulized hypertonic saline and recombinant human DNase in the treatment of pulmonary atelectasis in newborns. Pediatr Int. 2011 Jun;53(3):328-31. doi: 10.1111/j.1442-200X.2010.03245.x.
PubMed 20831650Prodhan P, Greenberg B, Bhutta AT, Hyde C, Vankatesan A, Imamura M, Jaquiss RD, Dyamenahalli U. Recombinant human deoxyribonuclease improves atelectasis in mechanically ventilated children with cardiac disease. Congenit Heart Dis. 2009 May-Jun;4(3):166-73. doi: 10.1111/j.1747-0803.2009.00289.x.
PubMed 19489944Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP. Nebulized hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006458. doi: 10.1002/14651858.CD006458.pub2.
PubMed 18843717Rosenfeld 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 22610452Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, Belousova EG, Xuan W, Bye PT; National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med. 2006 Jan 19;354(3):229-40. doi: 10.1056/NEJMoa043900.
PubMed 16421364Altunhan H, Annagur A, Pekcan S, Ors R, Koc H. Comparing the efficacy of nebulizer recombinant human DNase and hypertonic saline as monotherapy and combined treatment in the treatment of persistent atelectasis in mechanically ventilated newborns. Pediatr Int. 2012 Feb;54(1):131-6. doi: 10.1111/j.1442-200X.2011.03519.x.
PubMed 22114907Youness HA, Mathews K, Elya MK, Kinasewitz GT, Keddissi JI. Dornase alpha compared to hypertonic saline for lung atelectasis in critically ill patients. J Aerosol Med Pulm Drug Deliv. 2012 Dec;25(6):342-8. doi: 10.1089/jamp.2011.0954. Epub 2012 Mar 13.
PubMed 22413805
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nebulized Hypertonic Saline for Mechanically Ventilated Children
- ClinicalTrials.gov ID
- NCT01945944
- Acronym / sponsor ID
- 08-13-11
- Conditions
- Respiratory Failure
- Keywords
- pediatric, mucolytic, respiratory failure, atelectasis, hypertonic saline
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University Hospitals Cleveland Medical CenterUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Apr 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 19 Sep 2013 (estimated)
- Results
- Posted 28 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Children who need to be on a ventilator often have thick secretions/mucus in their lungs. These secretions can obstruct the breathing tube and their windpipe, which can worsen lung function and prolong the need for the ventilator. Hypertonic saline is a medicine that is used to thin out secretions in patients with cystic fibrosis (and other conditions). We hypothesize that having children on a ventilator inhale this medication will shorten the amount of time that they need to be on the ventilator.
Detailed description
Recent pediatric data shows that less than 80% of children mechanically ventilated for ≥ 96 hours survived to PICU discharge, while 100% of children mechanically ventilated for < 96 hours survived to PICU discharge. Interventions that decrease duration of mechanical ventilation may improve outcome by limiting ventilator-induced lung injury, sedative medication usage and ventilator-associated pneumonia. Obstructive airway secretions may prolong mechanical ventilation by causing atelectasis and endotracheal tube obstruction, with resultant cardio-respiratory instability. Nebulized hypertonic saline (HTS) is used to decrease mucus viscosity and increase mucociliary clearance in patients with diseases such as cystic fibrosis and bronchiolitis, and has been used to enhance airway clearance in mechanically ventilated children. Administering nebulized HTS to mechanically ventilated children may facilitate airway clearance and shorten mechanical ventilation.
In a randomized study of children < 2 years old following cardiac surgery, patients given dornase, another mucolytic agent, had a significantly decreased duration of mechanical ventilation versus those given saline placebo (52 hrs vs. 82 hrs). HTS may be even more effective, as mechanically ventilated newborns with persistent atelectasis had more improvement in radiographic findings and oxygen saturation when randomized to receive hypertonic saline compared to those randomized to receive dornase. This may be because dornase may only be effective in patients with leukocytes or bacterial present in tracheal aspirates, while HTS may be effective in all ventilated patients. Further study of the impact of prophylactic mucolytic therapy on the duration of mechanical ventilation in children is warranted.
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 |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo (0.9% saline)Placebo (0.9% saline), 3mL every 6 hrs for up to 7 days |
| Hypertonic Saline | Experimental | Drug: Hypertonic saline (3%)Hypertonic saline (3%), 3mL every 6hrs for up to 7 days |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- invasive mechanical ventilation of < 12 hrs duration prior to enrollment
- expected duration of mechanical ventilation of > 48hrs from enrollment
- age < 18yo
- cystic fibrosis
- status asthmaticus
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Hypertonic saline (3%)Also: 3% saline3mL of HTS given via nebulizer every 6hrs | Drug | Hypertonic Saline |
| Placebo (0.9% saline)Also: normal saline3mL of normal saline given via nebulizer every 6hrs | Drug | Placebo |
Primary outcome
Duration of Mechanical Ventilation
Time frame: typically 4 days - 2 weeks
8 secondary outcomes
Atelectasis
Time frame: during mechanical ventilation (typically 4 days - 2 weeks)
Wheezing
Time frame: during mechanical ventilation (typically 4 days - 2 weeks)
ICU Length of Stay
Time frame: during hospitalization (typically 4 days - 2 weeks)
Hospital Length of Stay
Time frame: during hospitalization (typically 4 days - 2 weeks)
Change in Serum Sodium From Baseline
Time frame: during hospitalization (typically 4 days - 2 weeks)
Dynamic Compliance
Time frame: during mechanical ventilation (typically 4 days - 2 weeks)
Oxygenation
Time frame: during mechanical ventilation (typically 4 days - 2 weeks)
Dead Space
Time frame: during mechanical ventilation (typically 4 days - 2 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21760567Payen V, Jouvet P, Lacroix J, Ducruet T, Gauvin F. Risk factors associated with increased length of mechanical ventilation in children. Pediatr Crit Care Med. 2012 Mar;13(2):152-7. doi: 10.1097/PCC.0b013e3182257a24.
- Background: PubMed 16265663Riethmueller J, Borth-Bruhns T, Kumpf M, Vonthein R, Wiskirchen J, Stern M, Hofbeck M, Baden W. Recombinant human deoxyribonuclease shortens ventilation time in young, mechanically ventilated children. Pediatr Pulmonol. 2006 Jan;41(1):61-6. doi: 10.1002/ppul.20298.
- Background: PubMed 20831650Dilmen U, Karagol BS, Oguz SS. Nebulized hypertonic saline and recombinant human DNase in the treatment of pulmonary atelectasis in newborns. Pediatr Int. 2011 Jun;53(3):328-31. doi: 10.1111/j.1442-200X.2010.03245.x.
- Background: PubMed 19489944Prodhan P, Greenberg B, Bhutta AT, Hyde C, Vankatesan A, Imamura M, Jaquiss RD, Dyamenahalli U. Recombinant human deoxyribonuclease improves atelectasis in mechanically ventilated children with cardiac disease. Congenit Heart Dis. 2009 May-Jun;4(3):166-73. doi: 10.1111/j.1747-0803.2009.00289.x.
- Background: PubMed 18843717Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP. Nebulized hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006458. doi: 10.1002/14651858.CD006458.pub2.
- Background: 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.
- Background: PubMed 16421364Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, Belousova EG, Xuan W, Bye PT; National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med. 2006 Jan 19;354(3):229-40. doi: 10.1056/NEJMoa043900.
- Background: PubMed 22114907Altunhan H, Annagur A, Pekcan S, Ors R, Koc H. Comparing the efficacy of nebulizer recombinant human DNase and hypertonic saline as monotherapy and combined treatment in the treatment of persistent atelectasis in mechanically ventilated newborns. Pediatr Int. 2012 Feb;54(1):131-6. doi: 10.1111/j.1442-200X.2011.03519.x.
- Background: PubMed 22413805Youness HA, Mathews K, Elya MK, Kinasewitz GT, Keddissi JI. Dornase alpha compared to hypertonic saline for lung atelectasis in critically ill patients. J Aerosol Med Pulm Drug Deliv. 2012 Dec;25(6):342-8. doi: 10.1089/jamp.2011.0954. Epub 2012 Mar 13.
- Individual participant dataSharing planned: No
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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.
Steven L Shein, MD principal investigator
University Hospitals Cleveland Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Hypertonic saline (3%) in people with Respiratory Failure, run by University Hospitals Cleveland Medical Center at 1 site in United States.
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 11 inclusion and 0 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 28 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Duration of Mechanical Ventilation (time frame: typically 4 days - 2 weeks). 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 NCT01945944, which also lists 9 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 28 Jun 2016.