Saline Hypertonic in Preschoolers + CT

NCT ID: NCT02950883

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-24
• Study Completion Date: 2021-06-25

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.

Detailed Description

Several observational studies have shown that cystic fibrosis (CF) patients less than or equal to 6 years of age have clinically silent airway damage. There is growing interest in early initiation of therapies to prevent or delay the progression of this lung disease in CF. In SHIP-CT, the investigators will evaluate treatment effects of HS relative to IS on measures of structural lung disease obtained from chest CT using a novel scoring system sensitive to early lung changes, the Perth-Rotterdam Annotated Grid Morphometric Analysis method for CF (PRAGMA-CF), that quantifies the volume percentage of diseased airways (%Dis), bronchiectasis (%Bx), and trapped air (%TA). As a secondary evaluation of structural airway damage, the investigators will use an image analysis system to measure airway dimensions relative to adjacent arteries (AA-system). Longitudinal changes in CT measures will also be compared to changes in lung function measured by the lung clearance index (LCI) obtained by N2 Multiple Breath Washout (MBW) and to clinical outcomes.

The primary hypothesis is that HS will reduce structural lung disease as assessed by the PRAGMA-CF computed tomography score relative to IS during the 48-week treatment period among preschool children with CF.

SHIP-CT is a parallel study to SHIP001 (ClinicalTrials.gov Identifier NCT02378467). The primary hypothesis of SHIP001, which runs in North America, is that compared to IS, HS will improve the LCI, a measure of ventilation heterogeneity, during the 48-week treatment period among preschool children with CF. The SHIP-CT study (SHIP002) will use a nearly identical study design as the SHIP001 study, with similar eligibility criteria and treatment arms, to determine whether HS reduces structural lung disease as measured by chest computed tomography (CT), in addition to stabilizing or improving functional outcomes as measured by LCI.

This is a multicenter, randomized, double-blind, controlled, parallel group trial assessing structural lung disease in children with CF ages 3 to 5 at enrollment. Participants will be randomized 1:1 to receive 7% hypertonic saline (treatment arm) vs. 0.9% isotonic saline (control arm) administered twice daily via jet nebulizer for 48 weeks. Study visits will occur at screening, enrollment, and at Weeks 12, 24, 36, and 48. Parents or the legal guardian will be contacted at Weeks 1, 4 and 8 to document changes in health status, adverse events, concomitant medications/treatments, and encourage study treatment compliance. Parents or the legal guardian will also be contacted approximately every 6 weeks between visit 3, 4, 5, and 6 to address individual issues or concerns related to study treatment or study participation, and to document changes in health status, medications and treatments.

Total duration of participant participation will be up to 53 weeks. As enrollment will occur over approximately 18 months, total duration of the study is expected to be up to 30 months (18 months enrollment plus 12 months for the last participants to complete study participation).

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active Treatment Group

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

Group Type: EXPERIMENTAL

Active Treatment Group 7% Hypertonic Saline

Intervention Type: 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

Control Group

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

Group Type: ACTIVE_COMPARATOR

Control Group 0.9% Isotonic Saline

Intervention Type: 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

Interventions

Active Treatment Group 7% Hypertonic Saline

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

Intervention Type: DRUG

Control Group 0.9% Isotonic Saline

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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:

1. A documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis (QPIT)

2. A documented genotype with two disease-causing mutations in the CFTR gene

2. Informed consent by parent or legal guardian

3. Age ≥ 36 months and ≤72 months at screening visit

4. Ability to comply with medication use, study visits and study procedures as judged by the site investigator

5. Ability to cooperate with chest CT at the enrollment visit as determined by the lung function technician

Exclusion Criteria

1. Chest CT within 8 months prior to the Screening visit

2. Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset within 3 weeks preceding screening or enrollment visit

3. Acute wheezing at screening or enrollment visit

4. Oxygen saturation < 95% (<90% in centers located above 4000 feet elevation) at screening or enrollment visit

5. Other major organ dysfunction, excluding pancreatic dysfunction

6. Physical findings that would compromise the safety of the participant or the quality of the study data as determined by site investigator

7. Investigational drug use within 30 days prior to screening or enrollment visit

8. Treatment with inhaled HS at any concentration within 30 days prior to screening or enrollment visit

9. 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

10. Chronic lung disease not related to CF

11. Inability to tolerate first dose of study treatment at the enrollment visit

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cystic Fibrosis Foundation

OTHER

Sponsor Role: collaborator

University of Washington, the Collaborative Health Studies Coordinating Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Harm Tiddens, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Centre, Rotterdam

Stephen Stick, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Telethon Kids Institute, Perth

Margaret Rosenfeld, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Seattle Children's Hospital, Seattle

Stephanie Davis, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University, Indianapolis

Felix Ratjen, MD, PhD, FRCPC

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Locations

Children's Hospital of Colorado

Aurora, Colorado, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Oregon Health Sciences University

Portland, Oregon, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Seattle Children's Hospital

Seattle, Washington, United States

Royal Women's and Children Hospital

Adelaide, , Australia

Lady Cilento Children's Hospital

Brisbane, , Australia

Royal Children's Hospital

Melbourne, , Australia

John Hunter Children's Hospital

Newcastle, , Australia

Children's Hospital at Westmead

Sydney, , Australia

Sydney Children's Hospital at Randwick

Sydney, , Australia

Perth Children's Hospital

West Perth, , Australia

Universitair Ziekenhuis Children's Hospital

Brussels, , Belgium

UZ Leuven - Gasthuisberg Ziekenhuis

Leuven, , Belgium

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Hospital for Sick Kids

Toronto, Ontario, Canada

Copenhagen University Hospital Rigshospitalet

Copenhagen, , Denmark

Hospice Civils de Lyon

Lyon, , France

Hospital Robert Debre

Paris, , France

Bambini Gesu Children's Hospital

Roma, , Italy

Ospedale Civile Maggiore

Verona, , Italy

Sophia Children's Hospital at Erasmus Medical Centre

Rotterdam, , Netherlands

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Countries

United States; Australia; Belgium; Canada; Denmark; France; Italy; Netherlands; Spain

References

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.

Reference Type: BACKGROUND

PMID: 25756857 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26359952 (View on PubMed)

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.

Reference Type: RESULT

PMID: 35286860 (View on PubMed)

Related Links

https://pubmed.ncbi.nlm.nih.gov/35286860/

Related Info

Other Identifiers

SHIP002

Identifier Type: -

Identifier Source: org_study_id