Deferoxamine in Aneurysmal Subarachnoid Hemorrhage Trial
Nyckelord
Abstrakt
Beskrivning
Aneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke affecting relatively young patients. It has an incidence of about 7 per 100,000. Associated economic costs are high. Treatment of the aneurysm to prevent rebleeding is the primary goal. Nevertheless, 3 to 12 days after the initial bleeding secondary ischemic changes occur in 30% of the patients. This delayed cerebral ischemia (DCI) remains the most important cause of mortality and morbidity in patients surviving aneurysm treatment.
Aneurysmal SAH exposes the brain to erythrocytes. Several days after the hemorrhage lysis of erythrocytes takes place and the brain is exposed to high concentrations of hemoglobin. Elevated hemoglobin concentrations are present not only at the basal surface of the brain, but also distributed around the brain and into deeper layers of the cortex. Heme is degraded by heme-oxygenase into carbon monoxide, biliverdin and iron. Free iron can react with H2O and O2- to form hydroxyl radicals (OH*). The generation of hydroxyl radicals in this cascade, known as the Haber-Weiss or Fenton reaction, leads to extraction of hydrogen from unsaturated lipids in the cell membrane and initiates lipid peroxidation. Additionally it can exacerbate excitotoxicity by increased intracellular iron accumulation.
Iron chelators remove the excess of iron and are standard care in iron-overloaded patients. The use of iron chelators for SAH has been subject of animal studies with promising results on reduced vasospasm, oxidative stress, neuronal cell death and mortality. No clinical study for the use of deferoxamine in aneurysmal subarachnoid hemorrhage has been performed. A safety study for the use of Deferoxamine in patients in intracerebral hemorrhage (which is distinct from subarachnoid hemorrhage) has been performed. There were no associated serious adverse events or mortality, Deferoxamine is a chelator is used for more than 40 years in patients with iron overload diseases. This study investigates the safety and tolerability of deferoxamine versus placebo in patients with SAH for 3 consecutive days.
Datum
| Senast verifierad: | 08/31/2017 |
| Först skickat: | 07/19/2016 |
| Beräknad anmälan inlämnad: | 08/21/2016 |
| Först publicerad: | 08/22/2016 |
| Senaste uppdatering skickad: | 09/25/2017 |
| Senaste uppdatering publicerad: | 09/27/2017 |
| Faktiskt startdatum för studien: | 11/30/2017 |
| Uppskattat primärt slutdatum: | 11/30/2017 |
| Beräknat slutfört datum: | 05/31/2018 |
Tillstånd eller sjukdom
Intervention / behandling
Drug: Treatment
Other: placebo
Fas
Armgrupper
| Ärm | Intervention / behandling |
|---|---|
| Experimental: Treatment Patients will be given deferoxamine 32 mg/kg/day (max iv rate 15 mg/kg/hr), patients with ferritin levels between 2,000 and 3,000 ng/ml will receive 32 mg/kg/day and patients with serum ferritin levels below 2,000 ng/ml wil receive 25 mg/kg/day. duration 3 days | Drug: Treatment Patients will be given deferoxamine 32 mg/kg/day (max iv rate 15 mg/kg/hr), patients with ferritin levels between 2,000 and 3,000 ng/ml will receive 32 mg/kg/day and patients with serum ferritin levels below 2,000 ng/ml wil receive 25 mg/kg/day.during 3 days |
| Placebo Comparator: placebo NaCl 0.9% in similar dosis to treatment arm | Other: placebo placebo (NaCl 0.9%) in equal dose to treatment |
Urvalskriterier
| Åldrar berättigade till studier | 18 Years Till 18 Years |
| Kön som är berättigade till studier | All |
| Accepterar friska volontärer | Ja |
| Kriterier | Inclusion Criteria: - subarachnoid hemorrhage diagnosed by CT on admission, - Randomizable within 72 hours of subarachnoid hemorrhage, - Saccular intracranial aneurysm proven by cerebral angiography or CTA, - Surgical or endovascular obliteration is performed, - Able to obtain written informed consent from patient or surrogate. - Patients in a good clinical grade (WFNS 1-3) Exclusion Criteria: - Pregnancy, as confirmed by routine urine test on admission, - Abnormal renal function at time of randomization (GFR <60 mL/min) - Elevated liver function test at time of randomization (AST > 45 U/L and ALT > 35 U/L.) - History of liver disease or active liver disease, Active renal disease, - Hypersensitivity to deferoxamine, - Patient taking medication not recommended for concomitant use with deferoxamine as per the product label (e.g. high dose vit. C medication). - Patients not able to complete the study follow-up the presence of 4 or more of the following exclusion criteria (risk modifiers for ARDS): - Tachypnea (respiratory rate >30) - SpO2 <95% - Obesity (BMI >30) - Acidosis (pH <7.35) - Hypoalbuminemia (albumin <3.5 g/dL) - concurrent use of chemotherapy |
Resultat
Primära resultatåtgärder
1. safety (drug related adverse events; i.e. renal and hepatic dysfunction) [6 months]
Sekundära resultatåtgärder
1. efficacy [6 months]
