Theophylline Effects in the Fontan Circulation (THIEF Pilot Study)

EU CT 2022-500301-41-00

A single group treatment phase 2 single-arm no-masking study to assess safety and efficacy of a short-term oral treatment with theophylline (ATC-no. R03D A04) in terms of improvements in cardiorespiratory fitness, health-related quality of life, cardiac performance and respiratory function in male and female adolescents aged 16 to 25 years with a Fontan-type surgical palliation of univentricular congenital heart disease.

2023-02-09

2023-09-15

2023-09-15

Completed

Early phase I

10

Inclusion Criteria: 1. Participants with univentricular congenital heart disease with a Fontan-type palliation 1. Who are able to perform all diagnostic and monitoring procedures necessary during trial period, in particular being able to perform a symptom-limited cardiopulmonary exercise test on an upright ergometer bicycle. 2. With available hepatic imaging results (ultrasound or magnetic resonance imaging) from less than 12 months before inclusion 3. Without biochemical indications of more than mild liver disease or liver failure (se exclusion criteria) of more than mildly reduced kidney function. 4. Considered and assessed eligible for administration of Theo-Dur® (theophylline) as specified in the SmPC. 2. Body mass index (BMI) within the range 18.5 - 34.9 kg/m2 (inclusive). 3. Contraceptive use by women is not under any national / local regulations in Norway. 1. Male participants: no restrictions. 2. Female participants: female participants should have a negative pregnancy test at inclusion and they receive information prior to consent that onset of pregnancy during treatment period has to be reported to the study team and leads to exclusion. 4. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. For participants \< 18 years, all (both) parents or caregivers with parental responsibilities have to sign the consent form in addition to the participant. Exclusion Criteria: 1. Current or previous (last 12 months) tachyarrhythmia which has been cause of medical investigation or hospitalization. 2. Heart rhythm during inclusion visit other than: * sinus rhythm or regular supraventricular rhythm (visible P-waves) regardless P-wave angle * nodal rhythm * isolated extra beats (supraventricular or ventricular) of a frequency considered clinically non-significant 3. Systemic hypertension (systolic or diastolic blood pressure above 95 percentile) 4. Biochemical signs of more than mild liver disease or liver failure indicated by one of the following: 1. INR \> 1.5 in the absence of warfarin treatment, 2. ALAT more than twice the upper normal limit 3. Bilirubin more than twice the upper normal limit 5. Imaging signs from the recent 12 months indicating more than mild Fontan-associated liver disease, indicated by imaging findings that need further diagnostic work-up to rule out hepato-cellular carcinoma 6. Biochemical indication of more than mildly reduced kidney function indicated by: a. Creatinine \> 150 μmol/L (male) or \> 120 μmol/L (female) 7. Pregnancy 8. Inherited forms of galactose intolerance (Lapp lactase deficiency or glucose-galactose malabsorption 9. Hypersensitivity to theophylline 10. Current treatment with pulmonary vasodilator medication (sildenafil, tadalafil, udenafil, bosentan, ambrisentan, macicentan, or any prostacyclin derivate) 11. Ongoing pharmacological treatment with the risk of drug-drug interactions. (Examples: cimetidine, quinolone derivates like enoxacin, ciprofloxacin, perfloxacin, viloxazine, macrolide antibiotics like erythromycin, troleandomycin, allopurinol, propranolol, disulfiram, isoniazid, oral contraceptives, flu vaccine, mexiletine, nifedipine, norfloxacin, ranitidin, tiabendazol, verapamil, fluvoxamine, carbamazepine, felodipine, phenobarbital, phenytoin, rifampicin, lithium, ketamine, glucagon) 12. Pregnancy or breastfeeding

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 10, 'type': 'ACTUAL'}}

2023-09-21