Saline Hypertonic in Preschoolers + CT

NCT02950883 | Completed Phase 2 DMC

• 1 other identifier: SHIP002
• Study Type: interventional
• Target: 116
• Locations: 9 countries
• Sites: 25

Brief Summary

The purpose of this study is to assess whether inhalation of 7% hypertonic saline (HS) twice daily for 48 weeks reduces structural lung disease as assessed by computed tomography (CT) in comparison with inhalation of 0.9% isotonic saline (IS) in preschool children (ages 3 to 6) with cystic fibrosis.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Hypertonic Saline; Inhaled Saline; Digestive System Diseases; Genetic Diseases, Inborn; Lung Diseases; Pancreatic Diseases; Pathologic Processes; Respiratory Tract Diseases; Computed Tomography (CT)

Outcome Measures

Primary Outcomes (1)

• Chest CT

  The difference in PRAGMA-CF %Dis between HS and IS study arm at end of study (48 weeks), adjusted for baseline, measured from standardized chest CT.

  48 weeks

Secondary Outcomes (3)

• PRAGMA-CF Sub-scores

  48 weeks

• Lung Clearance Index (LCI)

  48 weeks

• Cross-sectional and longitudinal relationships

  48 weeks

Study Arms (2)

Active Treatment Group

EXPERIMENTAL

7% Hypertonic Saline administered via inhalation twice daily for 48 weeks

Drug: Active Treatment Group 7% Hypertonic Saline

Control Group

ACTIVE COMPARATOR

0.9% Isotonic Saline administered via inhalation twice daily for 48 weeks

Drug: Control Group 0.9% Isotonic Saline

Interventions

Active Treatment Group 7% Hypertonic Saline DRUG

Drug: 7% Hypertonic Saline (HS) 4 mL of HS will be administered via inhalation twice daily for 48 weeks. The delivery system is a PARI Sprint Junior nebulizer with a PARI Baby face mask or mouthpiece driven by a PARI compressor (PARI Vios® Pro in USA, PARI BOY SX in Australia and Europe). Other Names: Hyper-Sal™, inhaled saline

Active Treatment Group

Control Group 0.9% Isotonic Saline DRUG

Drug: 0.9% Isotonic Saline (IS) 4 mL of IS will be administered via inhalation twice daily for 48 weeks The delivery system is the same as that for the test product. Other Names: Normal saline

Control Group

Eligibility Criteria

• Age: 3 Years - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of CF as evidenced by one or more clinical features consistent with the CF phenotype or positive CF newborn screen AND one or more of the following criteria:
• A documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis (QPIT)
• A documented genotype with two disease-causing mutations in the CFTR gene
• Informed consent by parent or legal guardian
• Age ≥ 36 months and ≤72 months at screening visit
• Ability to comply with medication use, study visits and study procedures as judged by the site investigator
• Ability to cooperate with chest CT at the enrollment visit as determined by the lung function technician

You may not qualify if:

• Chest CT within 8 months prior to the Screening visit
• Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset within 3 weeks preceding screening or enrollment visit
• Acute wheezing at screening or enrollment visit
• Oxygen saturation \< 95% (\<90% in centers located above 4000 feet elevation) at screening or enrollment visit
• Other major organ dysfunction, excluding pancreatic dysfunction
• Physical findings that would compromise the safety of the participant or the quality of the study data as determined by site investigator
• Investigational drug use within 30 days prior to screening or enrollment visit
• Treatment with inhaled HS at any concentration within 30 days prior to screening or enrollment visit
• Initiation (i.e. new prescription) of any inhaled hydrating agent such as mannitol or mucolytic agents such as dornase alpha within 30 days prior to the screening or enrollment visit
• Chronic lung disease not related to CF
• Inability to tolerate first dose of study treatment at the enrollment visit

Sponsors & Collaborators

• University of Washington, the Collaborative Health Studies Coordinating Center: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (25)

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Royal Women's and Children Hospital

Adelaide, Australia

Location

Lady Cilento Children's Hospital

Brisbane, Australia

Location

Royal Children's Hospital

Melbourne, Australia

Location

John Hunter Children's Hospital

Newcastle, Australia

Location

Children's Hospital at Westmead

Sydney, Australia

Location

Sydney Children's Hospital at Randwick

Sydney, Australia

Location

Perth Children's Hospital

West Perth, Australia

Location

Universitair Ziekenhuis Children's Hospital

Brussels, Belgium

Location

UZ Leuven - Gasthuisberg Ziekenhuis

Leuven, Belgium

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H3V4, Canada

Location

Hospital for Sick Kids

Toronto, Ontario, M5G1X8, Canada

Location

Copenhagen University Hospital Rigshospitalet

Copenhagen, Denmark

Location

Hospice Civils de Lyon

Lyon, France

Location

Hospital Robert Debre

Paris, France

Location

Bambini Gesu Children's Hospital

Roma, 00165, Italy

Location

Ospedale Civile Maggiore

Verona, 37126, Italy

Location

Sophia Children's Hospital at Erasmus Medical Centre

Rotterdam, Netherlands

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Related Publications (3)

• Rosenow T, Oudraad MC, Murray CP, Turkovic L, Kuo W, de Bruijne M, Ranganathan SC, Tiddens HA, Stick SM; Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF). PRAGMA-CF. A Quantitative Structural Lung Disease Computed Tomography Outcome in Young Children with Cystic Fibrosis. Am J Respir Crit Care Med. 2015 May 15;191(10):1158-65. doi: 10.1164/rccm.201501-0061OC.

  PMID: 25756857 BACKGROUND

• Ramsey KA, Rosenow T, Turkovic L, Skoric B, Banton G, Adams AM, Simpson SJ, Murray C, Ranganathan SC, Stick SM, Hall GL; AREST CF. Lung Clearance Index and Structural Lung Disease on Computed Tomography in Early Cystic Fibrosis. Am J Respir Crit Care Med. 2016 Jan 1;193(1):60-7. doi: 10.1164/rccm.201507-1409OC.

  PMID: 26359952 BACKGROUND

• Tiddens HAWM, Chen Y, Andrinopoulou ER, Davis SD, Rosenfeld M, Ratjen F, Kronmal RA, Hinckley Stukovsky KD, Dasiewicz A, Stick SM; SHIP-CT Study Group. The effect of inhaled hypertonic saline on lung structure in children aged 3-6 years with cystic fibrosis (SHIP-CT): a multicentre, randomised, double-blind, controlled trial. Lancet Respir Med. 2022 Jul;10(7):669-678. doi: 10.1016/S2213-2600(21)00546-4. Epub 2022 Mar 11.

  PMID: 35286860 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Cystic Fibrosis; Digestive System Diseases; Genetic Diseases, Inborn; Lung Diseases; Pancreatic Diseases; Pathologic Processes; Respiratory Tract Diseases

Interventions

Saline Solution, Hypertonic; Control Groups; Sodium Chloride

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hypertonic Solutions; Solutions; Pharmaceutical Preparations; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Harm Tiddens, MD, PhD

  Erasmus Medical Centre, Rotterdam

  PRINCIPAL INVESTIGATOR

• Stephen Stick, MD, PhD

  Telethon Kids Institute, Perth

  PRINCIPAL INVESTIGATOR

• Margaret Rosenfeld, MD, MPH

  Seattle Children's Hospital, Seattle

  PRINCIPAL INVESTIGATOR

• Stephanie Davis, MD

  Indiana University, Indianapolis

  PRINCIPAL INVESTIGATOR

• Felix Ratjen, MD, PhD, FRCPC

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2016
• First Posted: November 1, 2016
• Study Start: March 24, 2015
• Primary Completion: December 15, 2020
• Study Completion: June 25, 2021
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2); ES (1); US (7); DK (1); IT (2); AU (7); BE (2); NL (1); CA (2)