E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic intestinal failuyre (IF) is caused by large surgical bowel resection, severe motility, or absorption diseorders. These patientds require partial or total parenteral nutrition (PN and TPN, respectively) and are thereby critically dependent on maintaining venous acces withj central venous catheter (CVC). CVC-related thrombosis is a frequent and serious complication that leads to catheter failure and is associated with CVC-infections and sepsis. |
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E.1.1.1 | Medical condition in easily understood language |
Parenteral nutrition via central venous catheter is essential in patients unable to receive nutrition by oral intake or enteral tube feeding. Catheter-thrombosis is an important complication. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main aim of this study is to assess the clinical outcomes of this patient population treated with long-term parenteral nutrition and taking rivaroxaban and to relate these clinical outcomes to the laboratory assessments. The primary outcomes are the clinical outcomes after at least one year and the (variability in the) laboratory concentrations. |
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E.2.2 | Secondary objectives of the trial |
Secondary outcomes consist assessment of the quality of life in this patient population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosis of short bowel syndrome (<170 cm after Treitz ligamentum) or intestinal malabsorption, diagnosed by an endocrinologist in the AMC
- Current use of TPN
- Age 18 years or over
- Indication for anticoagulant therapy before the start of TPN (DOAC, vitamin K antagonist, heparin) such as stroke prevention in patients with atrial fibrillation, prevention of venous thromboembolic events
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E.4 | Principal exclusion criteria |
A potential subject who meets any of the following criteria will be excluded from participation in this study
- Symptomatic thrombosis at inclusion
- Major bleeding defined according to the International Society on Thrombosis and Haemostasis(11) in the 6 months prior to start participation
- Contraindication for direct oral anticoagulant
o Chronic treatment with NSAID/Cytochrome P450/PgP dependent co-
medication
o Severe renal (eGFR<15) or hepatic impairment (Child Pugh score B or C) o Pregnancy or inadequate use of contraception
- Gastrectomy or short bowel syndrome < 30 cm after Treitz ligamentum
- Medical or psychological condition that would not permit completion of the study or signing of informed consent, including life expectancy less than six months, or unwillingness to sign informed consent;
- Non-compliance or inability to adhere to treatment or to the follow-up visits.
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E.5 End points |
E.5.1 | Primary end point(s) |
i. Main study parameter/endpoint
Clinical outcomes after one year, related to the laboratory levels per subject:
* Efficacy: venous thromboembolism, cerebrovascular stroke
* Safety: (major) bleeding cfr. ISTH criteria, mortality
ii. Secondary study parameters/endpoints
* Inter- and intraindividual variability of rivaroxaban absorption
Laboratory outcomes:
* Correlation between anti Xa levels and rivaroxaban plasma concetrations as assessed by LC-MS/MS
Quality of life assessment
* SF-36 questionnaire
iii. Other study parameters
Baseline characteristics will be collected;
* Age
* Sex
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NL63863.018.18 Rivaroxaban in patients with Short Bowel Syndrome
* Underlying disease + severity score for SBS
* Risk factors for VTE or Cerebral stroke
* Co-morbidities
* Co-medication (relevant)
* Type and duration of anticoagulant treatment before switch to Rivaroxaban
* Estimated length of remaining bowel after surgical intervention
* Size, method of insertion catheter, thickness of lumen
* Duration, concentration and composition of nutrition
* Stoma production
* Diary for keeping record of stool
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- every three months after inclusion in the study, minimum one year, maximum two years in total.
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E.5.2 | Secondary end point(s) |
1) Laboratory outcomes:
* Inter- and intraindividual variability of rivaroxaban absorption
* Correlation between anti Xa levels and rivaroxaban plasma concetrations as assessed by LC-MS/MS
2) Quality of life assessment
* SF-36 questionnaire
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Laboratory outcomes:
- baseline = day of inclusion +/- 2 weeks: T=0, T=1 hour following first dose, T=2 hours following first dose, T=3, T=4, T=5, T=6 - 3 months after inclusion: T=0, T=1 hour following first dose, T=2 hours following first dose, T=3, T=4, T=5, T=6 - 6 months after inclusion: T=0, T=1 hour following first dose, T=2 hours following first dose, T=3, T=4, T=5, T=6
Quality of life assessment:
- baseline - 6 months after inclusion |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Prospective cohort drug study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |