Preventive Inhalation of Hypertonic Saline in Infants With Cystic Fibrosis

NCT01619657 | Completed Phase 2 DMC

• 1 other identifier: UKH-PIHSNC-1
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 4

Brief 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).

Conditions

Cystic Fibrosis Lung Disease

Keywords

Cystic Fibrosis; Hypertonic Saline; Infant; Newborn; Prevention

Outcome Measures

Primary Outcomes (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)

  during the 52 week treatment period

Secondary Outcomes (10)

• Rate of protocol-defined pulmonary exacerbations

  during the 52 week treatment period

• Time to first pulmonary exacerbation in both treatment groups

  during the 52 week treatment period

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

  during the 52 week treatment period

• Extent and severity of bronchial dilatation

  during the 52 week treatment period

• Proportion of children with impairments in lung function

  during the 52 week treatment period

Study Arms (2)

Hypertonic Saline

EXPERIMENTAL

Inhalation with 6% Hypertonic Saline twice daily over 1 year

Drug: 6% Hypertonic Saline (HS), 4mL

Isotonic Saline

ACTIVE COMPARATOR

Inhalation with 0.9% Isotonic Saline twice daily over 1 year

Drug: 0.9% Isotonic Saline (IS), 4mL

Interventions

6% Hypertonic Saline (HS), 4mL DRUG

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.

Also known as: MucoClear® 6%

Hypertonic Saline

0.9% Isotonic Saline (IS), 4mL DRUG

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.

Also known as: Normal Saline

Isotonic Saline

Eligibility Criteria

• Age: Up to 4 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Heidelberg University: lead
• German Center for Lung Research: collaborator

Study Sites (4)

University Children's Hospital Heidelberg, Cystic Fibrosis Centre

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

University Hospital Gießen and Marburg GmbH

Giessen, 35392, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

University Children's Hospital Schleswig-Holstein

Lübeck, 23538, Germany

Location

Related Publications (2)

• 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.

  PMID: 37319354 DERIVED

• 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.

  PMID: 30409023 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Saline Solution, Hypertonic; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Hypertonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions

Study Officials

• Marcus A Mall, MD

  University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: June 12, 2012
• First Posted: June 14, 2012
• Study Start: June 1, 2012
• Primary Completion: November 1, 2016
• Study Completion: October 1, 2017
• Last Updated: October 26, 2017

Record last verified: 2017-10

Locations

DE (4)