Theophylline Effects in the Fontan Circulation (THIEF Pilot Study)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Cardiorespiratory fitness
研究概览
简要总结
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.
详细描述
Single-group uncontrolled single-center open-label treatment study in adolescents (age 16-25 years) with univentricular congenital heart defects surgically palliated with a Fontan-type operation. Inclusion of eligible patients from inpatient and outpatient contacts at participating departments at Oslo University Hospital Rikshospitalet.
Study inclusion visit, drug treatment, remote dose adjustment, heart rhythm monitoring, and final post-treatment assessment study visit will be performed at the clinical research ward for children, Division of Paediatric and Adolescent Medicine.
Dose adjustment decisions and heart rhythm monitoring will be effectuated by the medical monitors (pediatric cardiology, cardiology) with continuous service through the entire study period.
Study duration: approximately 6 months (depending on inclusion progress, from inclusion of first participant until final visit of last enrolled participant) Individual treatment duration: minimum 12 weeks, maximum 15 weeks or until final study visit.
Visit frequency: two study visits, at inclusion and at end of treatment period (earliest after 12 weeks of treatment and latest after 15 weeks of treatment).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with univentricular congenital heart disease with a Fontan-type palliation
- •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.
- •With available hepatic imaging results (ultrasound or magnetic resonance imaging) from less than 12 months before inclusion
- •Without biochemical indications of more than mild liver disease or liver failure (se exclusion criteria) of more than mildly reduced kidney function.
- •Considered and assessed eligible for administration of Theo-Dur® (theophylline) as specified in the SmPC.
- •Body mass index (BMI) within the range 18.5 - 34.9 kg/m2 (inclusive).
- •Contraceptive use by women is not under any national / local regulations in Norway.
- •Male participants: no restrictions.
- •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.
- •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.
排除标准
- •Current or previous (last 12 months) tachyarrhythmia which has been cause of medical investigation or hospitalization.
- •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
- •Systemic hypertension (systolic or diastolic blood pressure above 95 percentile)
- •Biochemical signs of more than mild liver disease or liver failure indicated by one of the following:
- •INR > 1.5 in the absence of warfarin treatment,
- •ALAT more than twice the upper normal limit
- •Bilirubin more than twice the upper normal limit
- •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
- •Biochemical indication of more than mildly reduced kidney function indicated by:
- •a. Creatinine > 150 μmol/L (male) or > 120 μmol/L (female)
- •Inherited forms of galactose intolerance (Lapp lactase deficiency or glucose-galactose malabsorption
- •Hypersensitivity to theophylline
- •Current treatment with pulmonary vasodilator medication (sildenafil, tadalafil, udenafil, bosentan, ambrisentan, macicentan, or any prostacyclin derivate)
- •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)
- •Pregnancy or breastfeeding
研究组 & 干预措施
Treatment
12 week oral treatment (theophylline)
干预措施: Theophylline Tablets (Drug)
结局指标
主要结局
Cardiorespiratory fitness
时间窗: 12 weeks
Difference in oxygen uptake at anaerobic/ventilatory threshold pre/post treatment
Feasibility and safety - adverse events
时间窗: 12 weeks
Frequency of treatment emerged AE/SAE
Feasibility and safety - tolerability
时间窗: 12 weeks
Freedom from participant dropout based on tolerability of the study intervention
Feasibility and safety - drug dosing
时间窗: 12 weeks
Number of participants requiring dose reduction after first serum concentration
Feasibility and safety - arrhythmia
时间窗: 12 weeks
Freedom of arrhythmogenic side effects of the study treatment leading to patient dropout
次要结局
- Health-related quality-of-life(12 weeks)
- Health-related quality-of-life (SF 36)(12 weeks)
- Cardiac performance(12 weeks)
- Respiratory function(12 weeks)
- Sleep disordered breathing(12 weeks)
研究者
Thomas Möller
Principal investigator, MD PhD, senior consultant / senior researcher
Oslo University Hospital