MEANING
CREATING EVIDENCE FOR THE USE OF HYPERTONIC SALINE IN PEOPLE WITH PRIMARY CILIARY
DYSKINESIA – HELP-PCD
This interventional study investigates whether hypertonic saline solution treatment be used to improve mucus clearance and respiratory function in PCD patients
BACKGROUND
Primary Ciliary Dyskinesia (PCD) is an autosomal recessive genetic condition that causes defects in the function of cilia (a hair-like projection from the surface of a cell) resulting in airway obstruction with poor mucociliary clearance.
The restoration of mucus hydration may prove beneficial in improving lung function, reducing airway obstruction and altering lung morphology in adolescents and adults with PCD. The inhalation of hypertonic saline (a mixture of sodium chloride [NaCl]) is expected to draw water into the mucus, thereby hydrating secretions and leaving high concentrations of NaCl on airway surfaces.
The aim of the German Center for Lung Research (DZL)-funded study is therefore to provide proof of concept for the use of nebulized hypertonic saline (MucoClear® 6% Inhalation Solution; PARI Pharma GmbH) to improve Lung Clearance Index (LCI) (primary endpoint), lung function, quality of life, exercise capacity (secondary endpoints), exacerbations and lung morphology in people with PCD (pwPCD) (exploratory endpoints).
The clinical parameters to be assessed include:
- ventilation inhomogeneity (assessed by lung clearance index (LCI); the primary endpoint),
- lung function (assessed by percent predicted of forced expiratory volume in one second, ppFEV1; the secondary endpoint),
- time to first pulmonary exacerbation (an exploratory endpoint), and
- lung morphology (assessed by magnetic resonance imaging (MRI)- – an exploratory endpoint).
The study will provide data on the efficacy and safety of the hypersaline treatment, demonstrating its superiority over a normal saline solution.
STUDY OBJECTIVES
Hypertonic sodium chloride solution for patients with primary ciliary dyskinesia: What is the evidence?
Saline solution is also used in the treatment of HELP -PCD (primary ciliary dyskinesia). An interventional study now compares the benefits of hypertonic (6% NaCl) and isotonic saline solution (0.9%) in terms of improving mucus clearance and respiratory function in this indication.
Primary objective
- To evaluate efficacy of hypertonic saline (6% NaCl, sterile) inhalation in patients with PCD (pwPCD) aged ≥12 years based on improvement in LCI
Secondary objectives
- To determine the effect of hypertonic saline (6% NaCl, sterile) inhalation on lung function in pwPCD ≥12 years, by assessing the change in (percent predicted) forced expiratory volume in one second ((pp)FEV1), forced vital capacity ((pp)FVC) and forced (mid-) expiratory flow ((pp)FEF25-75)
- To determine the effect of hypertonic saline (6% NaCl, sterile) inhalation on the change in self-reported quality of life (QOL) by analyzing age-specific QOL–PCD, the modified Medical Research Council [mMRC] breathlessness scale and EQ-5D-5L questionnaires.
- To determine the effect of hypertonic saline (6% NaCl, sterile) inhalation on physical performance as measured by the increase in distance covered in the 6-minute walk test (6MWT)
Exploratory objective
To determine the effect of hypertonic saline (6% NaCl, sterile) for inhalation on time to first pulmonary exacerbation in pwPCD aged ≥12 years by comparing the mean time to first pulmonary exacerbation after day 0 in the intervention and control phases
Exploratory sub-studies
Sub-study I
Evaluation of non-contrast MRI of the lung as an endpoint for intervention studies in adult patients with PCD by analyzing the change in ventilated lung volume
Sub-study II
Establishing a biomaterial collection of pwPCD – as a part of routine clinical practice – for analysis in future translational research projects addressing aspects including pulmonary and systemic inflammation and the impact of the underlying genetic defect on molecular function.
TIME FRAMEWORK
01.05.2024 – 31.12.2026
NUMBER OF PATIENTS
Inclusion of 92 patients (≥ 12 years) with a PCD diagnosis
STUDY SITES
8-10 German university or non-university study centers with a well-established infrastructure and PCD-specific expertise.
STUDY TYPE/METHODOLOGY
Multi-center, randomized, double-blind, controlled, crossover, medical device proof-of-concept (PoC) trial, consisting of two treatment arms
STUDY DESIGN
Multicentre, randomised, double-blind, controlled, crossover, proof-of-concept (PoC) study with a medical device consisting of two treatment arms regarding the therapy of PCD with isotonic or hypertonic sodium chloride solution over a period of 28 weeks
Figure 1. HELP PCD Study design (V1, V2, V3 – visit 1, visit 2, visit 3 etc.)
Experimental intervention: Inhalation of hypertonic saline (6% NaCl) 4 ml twice daily via the eFlow® rapid inhalation system with eTrack Controller for 8 weeks
Control intervention: Inhalation of isotonic saline (0.9% NaCl) 4 ml twice daily via an eFlow® rapid inhalation system with eTrack Controller for 8 weeks
Run-in/Washout: Inhalation of isotonic saline (0.9% NaCl) 4 ml twice daily via an eFlow® rapid inhalation system with eTrack Controller for 4 weeks
In summary, the total participant duration will be 28 weeks, including a 4-week run-in/washout period, 2 sequential 8-week crossed-over phases separated by another 4-week run-in/washout period, and finally a 4-week follow-up period.
Statistical analysis of endpoints will include linear mixed models (LCI, ppFEV1, MRI etc.), time-to-event analysis for pulmonary exacerbations, and descriptive statistics/absolute numbers and relative frequencies.
PARTICIPATION OF CAPNETZ
CAPNETZ STIFTUNG is the sponsor of the study and is responsible for study management, biometrics, safety management, quality assurance, programming of the central data collection system, monitoring and data management and the final analysis of the study. CAPNETZ STIFTUNG is also responsible for all regulatory matters, such as ethics submission and registration of the study. The practical implementation of the DZL-funded HELP-PCD study is mainly carried out in close cooperation between the CAPNETZ STIFTUNG office and the participating DZL partner sites Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Berlin Institute of Health (BIH) of Charitè and Comprehensive Pneumology Center Munich (CPC-M).
Data collection and biomaterial collection are carried out by the CAPNETZ STIFTUNG in cooperation with the Hannover Unified Biobank (HUB) and the Institute for Diagnostic and Interventional Radiology at the MHH, as well as the DZL sites and other patient-recruiting clinics in Bochum, Jena and Münster.
The collected biosamples are available to DZL and CAPNETZ researchers and external partners on request via the CAPNETZ STIFTUNG for later analysis in the context of specific research questions. As PCD is a rare and under-researched disease, these biomaterials can be invaluable for translational research on PCD and bronchiectasis.
The electronic study management system (EDC) for central data collection is developed and maintained by Webspirit Systems GmbH, an ISO-9001 certified company, at the request of CAPNETZ STIFTUNG.