- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02615938
Hydroxychloroquin (HCQ) in Pediatric Interstitial Lung Disease (ILD) (HCQ-chILD-EU)
Hydroxychloroquine in Pediatric ILD: START Randomized Controlled in Parallel-group, Then Switch Placebo to Active Drug, and STOP Randomized Controlled in Parallel-Group to Evaluate the Efficacy and Safety of Hydroxychloroquine (HCQ)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Berlin, Germany, 13353
- Charité Berlin, Klinik für Pädiatrie
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Baden-Württemberg
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Tübingen, Baden-Württemberg, Germany, 72076
- Universitätsklinik für Kinder- und Jugendmedizin Tübingen
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Bayern
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München, Bayern, Germany, 80337
- Klinikum der Universität München, Haunersches Kinderspital
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Hessen
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Frankfurt, Hessen, Germany, 60590
- Universitätsklinikum Frankfurt, Pneumologie, Allergologie, Mukoviszidose
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Gießen, Hessen, Germany, 35385
- Justus-Liebig-Universität, Allgemeine Pädiatrie u. Neonatologie
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Niedersachsen
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Hannover, Niedersachsen, Germany, 30625
- Medizinische Hochschule Hannover
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Nordrhein-Westfalen
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Bochum, Nordrhein-Westfalen, Germany, 44791
- St. Joseph- und St. Elisabeth Hospital gGmbH
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Essen, Nordrhein-Westfalen, Germany, 45122
- Uniklinikum Essen, Pädiatrische Pneumologie
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Sachsen
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Leipzig, Sachsen, Germany, 04103
- Klinik u. Poliklinik für Kinder- u. Jugendmedizin der Universität Leipzig
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
Patients should be clinically stable during baseline (between Visit 1 and 2) for inclusion into the study
- To determine this, attending physicians can use SpO2 in room air for patients on room air or on O2-supplement; the absolute difference on SpO2 is expected not to be ≥ 5% between Visit 1 and 2. For patients on respiratory support, the summary key parameters should not change ≥ 20% between Visit 1 and 2 and
- No major changes in other medications between Visit 1 and 2
- Mature newborn ≥ 37 weeks of gestation, age ≥ 3 wks and <2y or Infants and children (≥2y and < 18y) or Adults (≥18 and ≤30y) or Previously preterm (≤ 37 weeks of gestation) babies or children and adults of all ages if chILD genetically diagnosed (see inclusion criterion 3.)
Diagnosis of chronic (≥ 3 wks of duration) diffuse parenchymal lung disease (DPLD = chILD), defined in at least one of the following ways:
- chILD genetically diagnosed Surfactant dysfunction disorders including patients with mutations in SFTPC, SFTPB, ABCA3, TTF1 (Nkx2-1), further extremely rare entities with specific mutations, for example in TBX4, NPC2, NPC1, NPB, COPA, LRBA and other genes. In this case, also previously preterm (≤ 37 weeks of gestation) babies or children and adults of all ages can be included into the study.
chILD histologically diagnosed
- Chronic pneumonitis of infancy (CPI)
- Desquamative interstitial pneumonia (DIP)
- Lipoid pneumonitis / Cholesterol pneumonia
- Nonspecific interstitial pneumonia (NSIP)
- PAP after the exclusion of mutations in GMCSF-Ra/b and GMCSF autoantibodies*
- Usual interstitial pneumonia (UIP)
- Follicular bronchitis/bronchiolitis/Lymphocytic interstitial pneumonia (LIP)
- Storage disease with primary pulmonary involvement (e.g. Niemann Pick)
- Hermansky-Pudlak Syndrome
- Idiopathic pulmonary haemorrhage (haemosiderosis)*
- Other histology diagnosing chILD, in particular combination of the above pattern, but not exclusively
- Start block: no HCQ treatment in the last 12 weeks Stop block: stable HCQ treatment for at least the last 12 weeks
- Ability of subject or/and legal representatives to understand character and individual consequences of clinical trial.
- Signed and dated informed consent of the subject (if subject has the ability) and the representatives (of underaged children) must be available before start of any specific trial procedures.
(*may be diagnosed in the absence of a lung biopsy by characteristic lung lavage cytology (PAS stain, Fe stain), CT pattern or autoantibodies (gliadin, endomysium; cANCA) and clinical course.)
Exclusion criteria:
Subjects presenting with any of the following criteria will not be included in the trial:
- chILD primarily related to developmental disorders
- chILD primarily related to growth abnormalities reflecting deficient alveolarisation
- chILD related to chronic aspiration
- chILD related to immunodeficiency
- chILD related to abnormalities in lung vessel structure
- chILD related to organ transplantation/organ rejection/GvHD
- chILD related to recurrent infections
- Acute severe infectious exacerbations
- Known hypersensitivity to HCQ, or other ingredients of the tablets (lactose-monohydrate, povidone, maize starch, magnesium stearate, hypromellose, macrogol or titanium dioxide (E 171), silicon dioxide or mannitol), to sucrose-octaacetate or sodium saccharine.
- Proven retinopathy or maculopathy
- Glucose-6-phosphate-dehydrogenase deficiency resulting in favism or hemolytic anemia
- Myasthenia gravis
- Hematopoetic disorders
- Pregnancy and lactation (Women with childbearing potential have to practice a medically accepted contraception during trial and till three months after the end of the treatment with HCQ, and a negative pregnancy test (serum or urine) should be existent on Visit 1, if girls of childbearing age and only if sexual relations are known or probable. It is at the discretion and responsibility of the attending physician to decide, whether a pregnancy test is necessary or not. Reliable contraception are systematic contraceptives (oral, implant, injection). Women that are sterile by surgery can participate in the trial. At the discretion of the investigator, sexual abstinence is also accepted as contraceptive method. Girls after menarche have to receive a counselling about birth control methods in presence of at least one parent, which has to be documented in the patient notes.
- Participation in other clinical trials during the present clinical trial or not beyond the time of 4 half-lives of the medication used, at least one week.
- Hereditary galactose intolerance, lactase deficiency or glucose-galactose- malabsorption
Renal insufficiency at screening, defined as glomerular filtration rate (GFR)
- < 40 mL/min/1.73 m2 in patients age 3 to 8 weeks
- < 60 mL/min/1.73 m2 in patients ≥ 8 weeks of age (KDIGO guideline 2012, K/DOQI guideline 2002)
- Liver disease, gastrointestinal disorder, haematological disorder, epilepsy or other neurological disorder, psoriasis, porphyria at the discretion of the treating physician
- Simultaneous prescription of other potentially nephrotoxic or hepatotoxic medication at the discretion of the treating physician
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Start HCQ block Verum
During trial: Hydroxychloroquine Sulfate (HCQ, Quensyl) in a loading dose of 10 mg/kg bw/d, p.o., one daily dose in the evening for 7 days, then reduction to 6,5 mg/kg bw/d for 3 weeks; the maximum daily dose is 400mg.
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Apply drug to modify lysosomal pH
Other Names:
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Placebo Comparator: Start HCQ block Placebo
At the beginning of the trial: Placebo for 4 weeks then Hydroxychloroquine Sulfate (HCQ, Quensyl) in a loading dose of 10 mg/kg bw/d, p.o., one daily dose in the evening for 7 days, then reduction to 6,5 mg/kg bw/d for 3 weeks; the maximum daily dose is 400mg.
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Apply Placebo not to modify lysosomal pH
Other Names:
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Experimental: Stop HCQ block Verum
Individual dose, usually Hydroxychloroquine Sulfate (HCQ, Quensyl) 6-10 mg/kg bw/d, p.o., one daily dose in the evening; the maximum daily dose is 400 mg.
The dose, on which the patient is included into the trial, should be continued for 3 months.
After therapy of 3 months the medication will be stopped.
The patients will be followed up for additional 3 months.
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Apply drug to modify lysosomal pH
Other Names:
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Placebo Comparator: Stop HCQ block Placebo
Patients will receive Placebo for 3 months and will be followed up for additional 3 months.
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Apply Placebo not to modify lysosomal pH
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change of Oxygenation
Time Frame: Start HCQ block: 28 and 56 days; Stop HCQ block: 84 days
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Start HCQ block: relative Change Trial day 1 through day 28 and relative Change day 28 to day 56; Change active compound compared to Change Placebo. Stop HCQ block: Relative change trail day 1 through day 84: change active compound compared to change Placebo. |
Start HCQ block: 28 and 56 days; Stop HCQ block: 84 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change of Oxygen Saturation
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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(O2-sat, in room air) (only absolute, as relative already Primary outcome)
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Change of Respiratory rate
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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(RR, in room air) (relative and absolute)
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Change of Retraction, Coughing
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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(yes/no)
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Change of Lab values
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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(GOT, Creatinine, gGT, blood count, differential, LDH, potassium, steady state drug level)
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Change of Oxygen demand
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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in room air, on Os-supplement or O2 flow
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Change of QoL
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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(PedsQl™ generic and chILD specific module)
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Change of Health economics
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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specific questionaire
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Change of Overall survival
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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death or not
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Change of Weight to Height ratio
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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Weight measured in kg and Height measured in cm
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Cumulative amounts of Steroid equivalents
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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Clinical course of lung disease (since last visit): Healthy/ Sick-better/ Sick-same/ Sick-worse/ Patient died
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Change of x-ray
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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if x-ray were done
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Change of pO2, pCO2
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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(capillary, in room air)
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Change of Pulmonary exacerbation
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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(since last visit)
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Change of Forced vital capacity
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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measured by spirometry or bodyplethysmography; If > 5y old (If a child ≤ 5 years is already able to perform the listed investigations (spirometry or bodyplethysmography), these should also be performed and documented at the discretion of the investigator.)
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Number of abnormal changes in Electrocardiographie (ECG)
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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measured on start and end of trial
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Change of 6 minute walking distance (6MWT) (in meter)
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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O2-saturation will be measured before and after 6MWT
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Change of Borg Scale
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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Measured after 6MWT
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Number of subjects with ophthalmologic abnormalities
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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Ophthalmologic review on start and end of trial
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Number of Treatment related advers events
Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days
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measured on each visit
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Start HCQ block: 28 days; Stop HCQ block: 84 days
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Matthias Griese, Prof., MD, Pediatric Pneumology, Ludwig-Maximilians-University Munich
- Principal Investigator: Elias Seidl, MD, Pediatric Pneumology, Ludwig-Maximilians University Munich
Publications and helpful links
General Publications
- Griese M, Kappler M, Stehling F, Schulze J, Baden W, Koerner-Rettberg C, Carlens J, Prenzel F, Nahrlich L, Thalmeier A, Sebah D, Kronfeld K, Rock H, Ruckes C; HCQ-study group, Wetzke M, Seidl E, Schwerk N. Randomized controlled phase 2 trial of hydroxychloroquine in childhood interstitial lung disease. Orphanet J Rare Dis. 2022 Jul 23;17(1):289. doi: 10.1186/s13023-022-02399-2.
- Griese M, Kohler 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- EudratCT:2013-003714-40
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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