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Cystic Fibrosis Lung DiseasePhase 2PRESISNCT01619657

Preventive Inhalation of Hypertonic Saline in Infants With Cystic Fibrosis

A Phase 2 study testing 6% Hypertonic Saline (HS), 4mL and 0.9% Isotonic Saline (IS), 4mL in people with Cystic Fibrosis Lung Disease, run by Heidelberg University at 4 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages Up to 4 months
Conditions the study is for
Cystic Fibrosis Lung Disease
What is being tested?
6% Hypertonic Saline (HS), 4mL and 0.9% Isotonic Saline (IS), 4mL
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
4 sitesGermany
Study dates
Jun 2012to Oct 2017
Phase
Phase 2
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 Up to 4 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.
  • Age at enrolment is 0 to 4 months.
  • 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).
  • Participation in this study is voluntary. Only patients, whose parents or legal guardians gave written consent, are included.

Who cannot join

  • Born < 30 weeks gestation.
  • Prolonged mechanical ventilation in the first 3 months of life.
  • A significant medical disease or condition other than CF likely to interfere with the child's ability to complete the entire protocol.
  • Previous major surgery except for meconium ileus.
  • Other major organ dysfunction, excluding pancreatic or hepatic dysfunction or another condition due to cystic fibrosis.
  • Physical findings that would compromise the safety of the subject or the quality of the study data as determined by investigator.
Show all 14Show fewer
  • History of adverse reaction to sedation.
  • Known hypersensitivity to study treatment.
  • 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.

Trial locations and contacts

4 sites in 1 country.

Germany4 sites

  • University Hospital Gießen and Marburg GmbH

    Giessen, 35392

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • University Children's Hospital Heidelberg, Cystic Fibrosis Centre

    Heidelberg, Baden-Wurttemberg, 69120

  • University Children's Hospital Schleswig-Holstein

    Lübeck, 23538

Other trials in Germany

About this study

Official title: Randomized, Double-blind, Controlled Pilot Study on Safety of Hypertonic Saline as Preventive Inhalation Therapy in Newborns and Infants With Cystic Fibrosis

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).

Read the 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.

Being tested
6% Hypertonic Saline (HS), 4mL, 0.9% Isotonic Saline (IS), 4mL
Keywords
Cystic Fibrosis, Hypertonic Saline, Infant, Newborn, Prevention
Medical subject headings
Cystic Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 6% Hypertonic Saline (HS), 4mLDrug

    Also called MucoClear® 6%

    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.

  • 0.9% Isotonic Saline (IS), 4mLDrug

    Also called Normal Saline

    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.

Study groups in NCT01619657
Study groupRoleWhat they receive
Hypertonic SalineExperimentalInhalation with 6% Hypertonic Saline twice daily over 1 year
Receives: Drug: 6% Hypertonic Saline (HS), 4mL
Isotonic SalineActive comparatorInhalation with 0.9% Isotonic Saline twice daily over 1 year
Receives: Drug: 0.9% Isotonic Saline (IS), 4mL

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of patients in both treatment groups with adverse events (AEs) and serious adverse events (SAEs)

    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)

    Measured: during the 52 week treatment period

Secondary outcomes (10)

  1. Rate of protocol-defined pulmonary exacerbations

    Rate of protocol-defined pulmonary exacerbations requiring treatment with oral, inhaled or intravenous antibiotics between subjects randomized to HS and IS

    Measured: during the 52 week treatment period

  2. Time to first pulmonary exacerbation in both treatment groups

    Measured: during the 52 week treatment period

  3. Proportion of children with morphological and/or functional changes due to CF lung disease at baseline and after 1 year of inhalation

    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)

    Measured: during the 52 week treatment period

  4. Extent and severity of bronchial dilatation

    Extent and severity of bronchial dilatation after MRI and CXR scores at baseline and after 1 year of inhalation in both groups

    Measured: during the 52 week treatment period

  5. Proportion of children with impairments in lung function

    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

    Measured: during the 52 week treatment period

  6. Severity of impairment in lung function test

    Severity of impairment in lung function test at baseline, after 3, 6, 9, and 12 months of inhalation in both groups

    Measured: during the 52 week treatment period

  7. Health-related quality of life

    Health-related quality of life as assessed by scores from Cystic Fibrosis Questionnaire - Revised Parent Report (CFQ-R, German version), administered quarterly

    Measured: during the 52 week treatment period

  8. Change in anthropometric and basic respiratory parameters

    Change in weight, height, body mass-index, weight-for-height, resting respiratory rate, and room air oxygen saturation

    Measured: during the 52 week treatment period

  9. Proportion of patients with new isolation of CF pathogen

    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

    Measured: during the 52 week treatment period

  10. Time to first isolation of a CF pathogen

    Time to acquisition of a CF pathogen is going to be compared between both treatment groups

    Measured: during the 52 week treatment period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jun 2012 (estimated)
  2. Study startJun 2012
  3. Primary completionNov 2016
  4. Study completionOct 2017

Resources

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 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01619657
Sponsor's protocol ID
UKH-PIHSNC-1
Acronym
PRESIS
Status last verified
Oct 2017
First submitted
12 Jun 2012
Last updated
26 Oct 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Wark P, McDonald VM, Smith S. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD001506. doi: 10.1002/14651858.CD001506.pub5.

    PubMed 37319354

  • Stahl M, Wielputz MO, Ricklefs I, Dopfer C, Barth S, Schlegtendal A, Graeber SY, Sommerburg O, Diekmann G, Husing J, Koerner-Rettberg C, Nahrlich L, Dittrich AM, Kopp MV, Mall MA. Preventive Inhalation of Hypertonic Saline in Infants with Cystic Fibrosis (PRESIS). A Randomized, Double-Blind, Controlled Study. Am J Respir Crit Care Med. 2019 May 15;199(10):1238-1248. doi: 10.1164/rccm.201807-1203OC.

    PubMed 30409023

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 6% Hypertonic Saline (HS), 4mL and 0.9% Isotonic Saline (IS), 4mL in people with Cystic Fibrosis Lung Disease, run by Heidelberg University at 4 sites in Germany.

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 7 inclusion and 14 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 26 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Germany. 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.

What does this phase mean?

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?

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?

Number of patients in both treatment groups with adverse events (AEs) and serious adverse events (SAEs) (time frame: during the 52 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 NCT01619657, 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 26 Oct 2017.

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