interstitial lung disease MedDRA version: 20.0 Level: PT Classification code 10022611 Term: Interstitial lung disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: hydrochloroquine
Pharmaceutical Form: Capsule
INN or Proposed INN: hydroxychloroquine
CAS Number: 118-42-3
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Conce
Sponsors
Klinikum der Ludwig-Maximilian-Universität München
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Patients should be clinically stable during baseline (between Visit 1 and 2) for inclusion into the study a) 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 b) No major changes in other medications between Visit 1 and 2 2)Mature newborn = 37 weeks of gestation, age = 3 wks and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 ?- hILD 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 capsules (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) o < 40 mL/min/1.73 m2 in patients age 3 to 8 weeks o < 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: START HCQ block To evaluate the efficacy of HCQ after 28 days of treatment in chILD compared to placebo. STOP HCQ block To evaluate the efficacy of HCQ after 84 days of treatment in chILD compared to Placebo ;Secondary Objective: START HCQ block - To evaluate the efficacy of HCQ after 56 days of treatment in chILD compared to 28 days. - To evaluate the safety of HCQ after 28 and 56 days of treatment in chILD. - To evaluate blood levels of HCQ after 28 and 56 days of treatment in chILD. STOP HCQ block - To evaluate the efficacy of chronic (> 3 months) HCQ treatment in chILD compared to placebo. - To evaluate the safety of HCQ after > 3 months of treatment in chILD. - To evaluate blood levels of HCQ before and after treatment in chILD ;Primary end point(s): START HCQ block Relative change trial day 1 (i.e. Visit 2) through day 28 (i.e. Visit 3) and relative change day 28 to day 56, (i.e. Visit 4): change active compound compared to change placebo STOP HCQ block Relative change trial day 1 (i.e. Visit 2) through day 84 (i.e. Visit 5): change active compound compared to change placebo ;Timepoint(s) of evaluation of this end point: 28/56 / 84 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - For both, START and STOP HCQ blocks absolute and relative change under the active compound from trial day 1 (i.e. Visit 2), to START block: day 28 (i.e. Visit 3), STOP block: day 84 (i.e. Visit 5) each, will be compared to change under placebo. The following variables will be investigated: - Oxygen saturation (O2-sat, in room air) (only absolute, as relative already primary outcome) - Respiratory rate (RR, in room air) (relative and absolute) - Retractions (yes/no) - Coughing (yes/no) - Oxygen demand - pO2, pCO2 (capillary, in room air) - Chest x-ray - Quality-of-life - Health economics - Overall survival - Weight for height - Cumulative amounts of steroid equivalents. Clinical course of lung disease (since last visit): Healthy/ Sick-better/ Sick-same/ Sick-worse/ Patient died - Pulmonary exacerbation (since last visit) 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.) The following lung function parameters will be assessed: FEV1 % predicted (recorded in L), FEV 1 (L), FVC % predicted (recorded in L), FVC (L); MEF 75 (L/s); MEF 50 (L/s); MEF 25 (L/s); TLC (L); ITGV (L); RV (L); R eff (kPa*s/L); R eff predicted (%). reference values according to the GLI 2012 lung function regression equations - 6 minute walking distance (meter) - O2-saturation before and after 6MWT - Borg scale - If ventilated: Duration (h) of mechanical ventilation NO (%), ECMO yes/no, if yes VA/VV, double lumen vs. single lumen, Flow-rate. - Safety monitoring Adverse events, clinical laboratory values (GOT, Creatinine, gGT, blood count, differential, LDH, potassium, steady state drug level), ECG, ophthalmologic review ;Timepoint(s) of evaluation of this end point: 56 / 84 days | — |
Countries
Austria, Germany, Italy, Poland, Portugal, Spain, Turkey, United Kingdom
Contacts
Public ContactMatthias Griese
Klinikum der Ludwig-Maximilian-Universität München
Outcome results
None listed