E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immobilization because of aneurysmal subarachnoidal haemorrhage (aSAH) with moderate-severe neurological deficits (e.g. hemiparesis) and reduced state of consciousness – equivalent to Hunt&Hess 4-5 – at the time of admission to ICU |
Immobilisation aufgrund einer aneurysmatischen Subarachnoidalblutung mit moderaten bis schweren neurologischen Defiziten (z.B.Hemiparese) aud reduziertem Bewusstsein – äquivalent Hunt&Hess 4-5 – zum Zeitpunkt der Aufnahme auf die Intensivstation |
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E.1.1.1 | Medical condition in easily understood language |
Immobilization because of reduced consciousness and neurological deficits because of an intracranial bleeding
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Immobilisation aufgrund von Bewusstseineintrübung und neurologischen Ausfällen bedingt durch eine Hirnblutung
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
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 |
twofold:
a) to evaluate if a single administration of denosumab decreases bone resorption (CTX-1) within one month in immobilized patients
b) to evaluate if one year of denosumab therapy has a positive effect on the immobilization-associated bone loss. (hip region) Additionally, potential changes of BTMs will be evaluated.
Pilot study (n=14):
evaluate if a single administration of denosumab decreases bone resorption (CTX-1) within one month in immobilized patients |
zweifach:
a) Änderung des Serumspiegles von CTX-1 zwischen Baseline und 1 Monat nach erster Denosumab-Gabe
b) Änderung der Knochenmineraldichte der Hüftregion ein Jahr nach erster Denosumab-Gabe
Pilotstudie (n=14):
Änderung des Serumspiegles von CTX-1 zwischen Baseline und 1 Monat nach Denosumab-Gabe |
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E.2.2 | Secondary objectives of the trial |
a) Serum levels of osteocalcin (Oc), bone-spcific alkaline Phosphatase (BAP), procollagen ta) pe 1 amino-terminal propeptide (P1NP), Tartate resistante acid phosphatase (TRAP), dickkopf 1 (DKK1), sclerostin (SOST), periostin (PSTN), 24-h urine: Ca excretion one month and twelve months after 1st denosumab application
b) BMD: T-score lumbar spine twelve months after 1st denosumab application
c) Reasons for drop outs
Pilot study (n=14):
cortical thickness and density index of the proximal tibia (quantitative ultrasound) - characterization of subjects |
a) Serum piegel von Osteokalzin (Oc), knochen-spezifischer alkalischer Phosphatase (BAP), Prokollagen Typ 1 amino-terminales Propeptid (P1NP), Tartat resistente sauere Phosphatase (TRAP), Dickkopf 1 (DKK1), Sklerostin (SOST), Periostin (PSTN), 24-h Harn: Ca Ausscheidung ein Monat und 12 Monate nach erster Denosumab-Gabe
b) KMD: T-Score der LWS 12 Monate nach erster Denosumab-Gabe
c) Gründe für Studienabbruch
Pilotstudie (n=14):
Kortikale Dicke und Dichteindex an der proximalen Tibia (Quantitative Ultraschallmessung) - zur Charakterisierung des Kollektivs |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Women, men
30-80 years of age
Patients after aneurysmal subarachnoidal haemorrhage (aSAH) with moderate-severe neurological deficits (e.g. hemiparesis) and reduced state of consciousness – equivalent to Hunt&Hess 4-5 – at the time of admission to ICU
Normal liver function
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Frauen und Männer
30-80 Jahre
Patienten, die aufgrund einer Hirnblutung bei Aufnahme auf der Intensivstation moderate bis schwere neurologische Defizite und eine eingeschränkte Bewusstseinslage haben (Hunt&Hess 4-5)
Normale Leberfunktion
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E.4 | Principal exclusion criteria |
Patients after aneurysmal subarachnoidal haemorrhage (aSAH; Hunt&Hess 0-3)
Patients after intracerebral bleeding
Subjects with a history of prior solid organ transplantation
Cancer within the previous 5 years
Pregnancy
Rheumatoid arthritis
Severe renal insufficiency (CKD V)
Intake of drugs with potential effects on BMD like lithium, estrogen-replacement therapy, selective estrogen-receptor modulators (SERMS), oral bisphosphonates in the last three months, denosumab and parenteral bisphosphonates in the last year - except medication necessary for the underlying disease
Non-osteoporotic bone disease
Recent fragility fracture within 6 months
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Patienten nach aneurysmatischer Subarachnoidalblutung (aSAH; Hunt&Hess 0-3)
Patients nach intrazerebraler Blutung
Personen nach solider Organtransplantation
Malignom innerhalb der letzten 5 Jahre
Schwangerschaft
Rheumatoide Arthritis
Schwere Niereninsuffizienz(CKD V)
Einnahme von Medikamenten mit potentiellem Effekt auf die Knochenmineraldichte wie Lithium, Hormonersatztherapie, Selektive Östrogen-Rezeptor Modulatoren (SERMS), orale Bisphosphonate in vergangenen 3 Monaten, Denosumab und parenterale Bisphosphonates im vergangeen Jahr - ausgenommen Medikation welche aufgrund der Grunderkrankung nötig ist
Nicht-osteoporotische Knochenerkrankung
Fragilitätsfraktur innerhalb der letzten 6 Monate
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E.5 End points |
E.5.1 | Primary end point(s) |
a) Serum levels of carboxy-terminal collagen crosslinks (CTX-1) one month after first denosumab application
b) BMD of the hip region one year after the first denosumab application
Pilot study (n=14):
Serum levels of carboxy-terminal collagen crosslinks (CTX-1) one month after denosumab application |
a) Serumspiegel von Carboxy-terminalen Kollagen Crosslinks (CTX-1) ein Monat nach erster Denosumab-Gabe
b) KMD der Hüftregion of the hip region ein Jahr nach erster Denosumab-Gabe
Pilotstudie (n=14):
Serumspiegel von Carboxy-terminalen Kollagen Crosslinks (CTX-1) ein Monat nach Denosumab-Gabe |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
a) CTX-1: before first denosumab application, one month after first denosumab application
b) BMD: one month and 12 months after first denosumab application
Pilot study (n=14):
cortical thickness and density index of the proximal tibia (quantitative ultrasound): within one week after baseline |
a) CTX-1: vor erster Denosumab-Gabe, ein Monat nach erster Denosumab-Gabe
b) KMD: ein Monat und 12 Monate nach erster Denosumab-Gabe
Pilotstudie (n=14):
CTX-1: vor Denosumab-Gabe, ein Monat nach Denosumab-Gabe |
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E.5.2 | Secondary end point(s) |
a) Serum levels of osteocalcin (Oc), bone-spcific alkaline Phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP), Tartate resistante acid phosphatase (TRAP), dickkopf 1 (DKK1), sclerostin (SOST), periostin (PSTN), 24-h urine: Ca excretion one month and twelve months after 1st denosumab application
b) BMD: T-score lumbar spine twelve months after 1st denosumab application
c) Reasons for drop outs
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a) Serumspiegel von Osteokalzin (Oc), knochen-spezifischer alkalischer Phosphatase (BAP), Prokollagen Typ 1 amino-terminales Propeptid (P1NP), Tartat resistente sauere Phosphatase (TRAP), Dickkopf 1 (DKK1), Sklerostin (SOST), Periostin (PSTN), 24-h Harn: Ca Ausscheidung ein Monat und 12 Monate nach erster Denosumab-Gabe
b) KMD: T-Score der LWS 12 Monate nach erster Denosumab-Gabe
c) Gründe für Studienabbruch
Pilotstudie (n=14):
Kortikale Dicke und Dichteindex an der proximalen Tibia (Quantitative Ultraschallmessung) - innerhalb einer Woche nach Baseline
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Biochemical parameters: before first denosumab application, one month, 6 and 12 months after first denosumab application
BMD: one month and 12 months after first denosumab application
Reasons for drop outs: on occasion
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Laborparameter: vor erster Denosumab-Gabe, ein Monat, 6 und 12 Monate nach erster Denosumab-Gabe
KMD: ein Monat und 12 Monate nach erster Denosumab-Gabe
Gründe für Studienabbruch: anlassbezogen
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |