Primary Objective: Proof of safety and tolerability of home parenteral nutrition (HPN) with an Omega-3 fatty acid enriched MCT/LCT lipid emulsion in adult patients with chronic intestinal failure (CIF) in need of long-term HPNSecondary Objectives:…
ID
Source
Brief title
Condition
- Malabsorption conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of the study is the change of liver function parameters
defined as the sum of the N(0,1)-transformed differences in
bilirubin, Alanine transaminase (ALT) and Aspartate transaminase (AST) from
baseline to visit 2.
Secondary outcome
Variables indicated with * are calculated values
Safety
Hepatic function
* Bilirubin
* Alanine transaminase (ALT)
* Aspartate transaminase (AST)
* AST/ALT ratio*
* Alkaline phosphatase (ALP)
* Gamma-glutamyl transpeptidase (GGT)
Blood count and coagulation
* White blood cells (WBCs)
* Red blood cells (RBCs)
* Hemoglobin (Hb)
* Hematocrit (Hct)
* Platelets
* International normalized ratio (INR) (if not possible prothrombin time [PT =
Quick-value] is accepted)
* Activated partial thromboplastin time (aPTT)
Other biochemical parameters
* Blood glucose
* Electrolytes (Na, Cl, K, Ca, Mg, P)
* Serum creatinin
* Triglycerides
* Cholesterol
* High-density lipoprotein (HDL)
* Low-density lipoprotein (LDL)
* C-reactive protein (CRP)
* α-Tocopherol/Vitamin E (facultative if routinely assessed)
* Triene:tetraene ratio* obtained from fatty acid pattern in serum
Adverse events (AEs)
Efficacy
• Fatty acid pattern in serum and RBCs
• BMI*
Other variables
• Demographic data
o Age
o Gender
o Ethnic origin
o Body height
o Body weight
Anamnesis
• Medical history relevant with regard to HPN
o Pathological classification of IF
o Underlying diseases
• Concomitant disease(s)
• Ongoing medications
• Lipid emulsion(s) during the last 6 months
• Anamnestic peculiarities
• Physical examination
• Vital signs
• Body weight change*
• Quality of life (EQ-5DTM)
• Concomitant medication
• Energy requirements
• PN regimen prescription
• Treatment compliance*
• Intake of oily fish meals
• Study termination
Background summary
Several studies have demonstrated beneficial effects of modern LEs containing
Omega-3 FA in various patient groups, e.g. in critically-ill and
gastrointestinal surgery patients. Thus far, the evidence on the use of
Omega-3-PUFA LEs in HPN patients is still low. Due to this low evidence the
recommendation for use of the n-3 enriched LE Lipidem is limited to 7 days. If
medically indicated the lipid emulsion may be administered over longer periods
with appropriate metabolic monitoring. Since most patients in need of
long-term/life-long HPN receive lipids, it is of great importance to use a LE
that provides sufficient amounts of EFA but without straining liver function.
Studies on pediatric and adult HPN patients demonstrated that the use of a
novel combination LE containing fish-oil is safe and yielded lower levels of
bilirubin and/or transaminases compared to soybean-based lipid. Although the
results are promising, their explanatory power is limited with only 4 weeks of
treatment.
In this study, we want to compare Lipidem with a LCT/MCT LE (Lipofundin MCT)
with regard to integrity of liver function in HPN patients with extended
treatment duration. In line with the available literature we will consider
biochemical markers for the assessment of
liver function, in particular AST, ALT and bilirubin for the primary analysis
(Cavicchi et al., 2000; Klek et al. 2013; Tillman 2013). In this study HPN
patients with CIF (IF Type III) will be considered and cancer patients will be
excluded in order to have a largely homogenous patient population. This is
because the medical instability of cancer patients related to their disease
and/or anti-cancer treatment might tamper possible
nutrition related findings.
Aim of the study is to demonstrate non-inferiority of Lipidem against
Lipofundin MCT and consequently to proof of its safety and tolerability in the
treatment of HPN patients for a projected period of 8 weeks.
Study objective
Primary Objective: Proof of safety and tolerability of home parenteral
nutrition (HPN) with an Omega-3 fatty acid enriched MCT/LCT lipid emulsion in
adult patients with chronic intestinal failure (CIF) in need of long-term HPN
Secondary Objectives: Further safety and efficacy evaluation
Study design
This is a prospective, randomized, controlled, double-blind, multicenter phase
IV clinical trial performed in two parallel groups.
Intervention
Comparison will be made of an Omega-3-FA enriched MCT/LCT lipid emulsion
(Lipidem) with a MCT/LCT lipid emulsion (Lipofundin MCT). The IP will be
administered intraveniously.
Patients will be randomized at a 1:1 ratio to receive either the
investigational test product or the investigational reference product.
The IP will be delivered as the lipid part of the PN and will be administered
according to the individual patient*s normal prescription. The projected
duration of IP treatment will be 8 weeks. Assessments will be done at baseline,
visit 1 and visit 2. Thereafter, the study is terminated for the individual
patient.
Study burden and risks
Both investigational products (IPs) have market authorization in various
countries worldwide.
With regard to dosage and infusion rates the proposed use of IPs will be
according to the registered Summaries of Product Characteristics (SmPCs).
However, for the investigational test product Lipidem the evidence for
long-term use is yet only low, whereby the recommendation for use is limited to
7 days.
The reference product Lipofundin MCT - as well as other LCT and LCT/MCT lipid
emulsions - is used for the treatment of HPN patients since many years.
For both IPs there are potential undesirable effects, of which most are very
rare under conditions of correct use in terms of dosage, monitoring,
observation of safety restrictions and instructions. Given that patients of the
intended population are dependent on nutritional treatment and the
supply of lipids, the risks associated with the participation in the study are
not higher than those that are assumed when lipids are administered in regular
treatment.
Stable HPN patients usually visit their discharging hospital (HPN center) every
2-4 months for regular monitoring, which includes laboratory blood sample
analysis. In the course of the study the monitoring intervals will be shorter,
which necessitates two extra visits. During those extra visits, blood samples
will be obtained for analysis of routine laboratory parameters as well.
Furthermore, blood samples for special
laboratory analysis, i.e. fatty acid pattern analysis, will be taken at
baseline and visit 2.
In total 70 ml blood will be obtained from the patient for the entire study.
Due to the two extra study visits, participation might enhance the risks that
are related with travelling activities.
All assessments that are performed during this study are corresponding to
clinical practice and are carried out by trained personnel with proper
equipment. The correlated risks are regarded as minimal. Moreover, the closer
monitoring during the study course ensures the optimal supervision of the
clinical status and the nutritional support of the patient, which can be
regarded as benefit.
Carl-Braun-Straße 1
Melsungen 34212
DE
Carl-Braun-Straße 1
Melsungen 34212
DE
Listed location countries
Age
Inclusion criteria
1. Signed informed consent available
2. Male or female patients >= 18 years of age
3. Patients with chronic intestinal failure receiving HPN including lipids in
whom
the parenteral macronutrients have not been changed by more than 10% for
at least 3 months
4. Patients receiving >= 3.0 g lipids/kg body weight per week
Exclusion criteria
1. Persistent high total bilirubin values in medical history of the last 6
months
(> 40µmol/l)
2. Patients in whom PN was interrupted for longer than 4 continuous weeks in
the preceding 6 months
3. Patients with history of cancer and anti-cancer treatment within the last
2 years
4. Hypersensitivity to egg, fish or soya-bean protein or to any of the active
substances or excipients
5. Patients treated in the past or currently with Teduglutide
6. Contraindications to investigational products (if available from medical
records) including:
- Severe hyperlipidemia, including severe hypertriglyceridaemia (>= 1000
mg/dl or 11.4 mmol/l)
- Severe coagulopathy
- Intrahepatic cholestasis
- Severe hepatic insufficiency
- Severe renal insufficiency in absence of renal replacement therapy
- Acute thromboembolic events
- Fat embolism
- Aggravating haemorrhagic diatheses
- Metabolic acidosis
7. General contraindications to parenteral nutrition (if available from medical
records) including:
- Unstable circulatory status with vital threat (states of collapse and shock)
- Acute phase of cardiac infarction or stroke
- Unstable metabolic conditions (e.g. decompensated diabetes mellitus,
severe sepsis, coma of unknown origin)
- Inadequate cellular oxygen supply
- Disturbances of the electrolyte and fluid balance (e.g. hypokalaemia and
hypotonic dehydration)
- Acute pulmonary edema
- Decompensated cardiac insufficiency
8. Positive test for HIV, Hepatitis B or C (from medical history)
9. Known or suspected drug or alcohol abuse
10. Patients who are unwilling or mentally and/or physically unable to adhere to
study procedures
11. Participation in another interventional clinical trial in parallel or
within three
months prior to the start of this clinical trial
12. Any medical condition that in the opinion of the investigator might put the
subject at risk or interfere with patients participation
For women with childbearing potential (i.e. females who are not chemically or
surgically sterile or females who are not post-menopausal)
13. Women of childbearing potential tested positive on standard pregnancy test
(urine dipstick)
14. Lactation
15. Women of childbearing potential who do not agree to apply adequate
contraception
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-000849-23-NL |
| CCMO | NL59956.091.17 |