A protocol design for the study of hydroxychloroquine and children with interstitial lung disease

Interstitial lung disease (chILD) in children is rare and consists of many distinct entities affecting the lung parenchyma, resulting in chronic lung disease
.
The natural history of many of these diseases is associated with high morbidity and significant mortality
.
Symptomatic treatment includes supplemental oxygen, adequate nutrition to accommodate high energy demands due to the increased respiratory effort required, and immunization against respiratory pathogens to prevent exacerbations from respiratory infections
.
To date, there is no proven drug treatment
.
This placebo-controlled study was designed to evaluate the efficacy and safety of hydroxychloroquine in middle-term children
.

Schematic study setup:

Methods and design: This study was an exploratory, prospective, randomized, double-blind, placebo-controlled study of hydroxychloroquine (HCQ) in children
.
Patients may be enrolled when diagnosed with chronic (≥3 weeks duration) diffuse parenchymal lung disease (chILD) genetically defined, histologically defined, or diagnosed with idiopathic pulmonary hemorrhage (hemosiderosis)
.
The study consists of two distinct study blocks, a START and a STOP block, which can be started in any order
.
Each patient can only participate in each block once
.
In the START module, subjects were randomly assigned to a parallel group for 4 weeks of treatment, and then the placebo group was switched to the active drug
.
In the STOP module, subjects taking HCQ were randomized into parallel groups treated with placebo or HCQ
.

Treatment responders (changes in oxygenation) are defined according to the patient's condition:

Discussion: This study is the first international, investigator-initiated, prospective and controlled study of pharmacotherapy in children
.
The advantage of choosing to use this type of study block design is that it allows for the inclusion of patients who are on or have discontinued treatment with HCQ, thereby allowing the participation of patients who have previously started off-label use of HCQ
.
The crossover design and selected outcome parameters allowed us to include appropriate numbers of patients of all age groups, from neonates to adults with these rare diseases
.

Inclusion criteria for patient participation in the study:

Trial Registration: This is an exploratory, phase 2a, randomized, double-blind, placebo-controlled, parallel group, multinational study investigating the initiation or cessation of hydroxychloroquine use in pediatric subjects
.
STUDY TITLE: Hydroxychloroquine in Pediatric ILD: START Parallel Group Randomized Control, Then Placebo Switched to Active, STOP Parallel Group Randomized Control to Evaluate the Efficacy and Safety of Hydroxychloroquine (HCQ)
.

References: Griese M, Köhler M, Witt S, Sebah D, Kappler M, Wetzke M, Schwerk N, Emiralioglu N, Kiper N, Kronfeld K, Ruckes C, Rock H, Anthony G, Seidl E.
Prospective evaluation of hydroxychloroquine in pediatric interstitial lung diseases: Study protocol for an investigator-initiated, randomized controlled, parallel-group clinical trial.
Trials.
2020 Apr 3;21(1):307.
doi: 10.
1186/s13063-020-4188-4.
PMID: 32245508 ; PMCID: PMC7118852.