scholarly journals CompLement C5 Antibodies for decreasing brain injury after aneurysmal Subarachnoid Haemorrhage (CLASH): study protocol for a randomised controlled phase II clinical trial

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Inez Koopman ◽  
◽  
Gabriel J. E. Rinkel ◽  
Mervyn D. I. Vergouwen
Keyword(s):  
Clinical Trial ◽  
Brain Injury ◽  
Subarachnoid Haemorrhage ◽  
Phase Ii ◽  
Intervention Group ◽  
Case Fatality ◽  
Phase Ii Clinical Trial ◽  
Aneurysmal Subarachnoid Haemorrhage ◽  
Efficacy And Safety ◽  
Randomised Controlled

Abstract Background The inflammatory response after aneurysmal subarachnoid haemorrhage (aSAH) has been associated with early brain injury, delayed cerebral ischaemia, poor functional outcome, and case fatality. In experimental SAH studies, complement C5 antibodies administered shortly after SAH reduced brain injury with approximately 40%. Complement component C5 may be a new therapeutic target to reduce brain injury and hereby improve the outcome after aSAH. We aim to investigate the pharmacodynamic efficacy and safety of eculizumab (complement C5 antibody) in patients with aSAH. Methods A randomised, controlled, open-label, phase II clinical trial with blinded outcome assessment. Eculizumab (1200 mg) is administered intravenously < 12 h, on day 3 and on day 7 after ictus. Patients in the intervention group receive prophylactic antibiotics for 4 weeks, and those with a central line or an external ventricular shunt and a positive fungal or yeast culture also receive prophylactic antifungal therapy for 4 weeks. The primary outcome is C5a concentration in the cerebrospinal fluid (CSF) on day 3 after ictus. Secondary outcomes include the occurrence of adverse events, inflammatory parameters in the blood and CSF, cerebral infarction on magnetic resonance imaging, and clinical and cognitive outcomes. We aim to evaluate 26 patients with CSF assessments, 13 in the intervention group and 13 in the comparator group. To compensate for early case fatality and inability to obtain CSF, we will include 20 patients per group. Discussion The CLASH trial is the first trial to investigate the pharmacodynamic efficacy and safety of eculizumab in the early phase after aSAH. Trial registration Netherlands Trial Register NTR6752. Registered on 27 October 2017 European Clinical Trials Database (EudraCT) 2017-004307-51

scholarly journals CompLement C5 Antibodies for decreasing brain injury after aneurysmal Subarachnoid Haemorrhage (CLASH): study protocol for a randomized controlled phase II clinical trial

2020 ◽  
Author(s):  
Inez Koopman ◽  
Gabriel J.E. Rinkel ◽  
Mervyn D.I. Vergouwen
Keyword(s):  
Clinical Trial ◽  
Brain Injury ◽  
Subarachnoid Haemorrhage ◽  
Phase Ii ◽  
Intervention Group ◽  
Case Fatality ◽  
Phase Ii Clinical Trial ◽  
Aneurysmal Subarachnoid Haemorrhage ◽  
Efficacy And Safety ◽  
Randomized Controlled

Abstract Background The inflammatory response after aneurysmal subarachnoid haemorrhage (aSAH) has been associated with early brain injury, delayed cerebral ischemia, poor functional outcome, and case-fatality. In experimental SAH studies, complement C5 antibodies administered shortly after SAH reduced brain injury with approximately 40%. Complement component C5 may be a new therapeutic target to reduce brain injury and hereby improve outcome after aSAH. We aim to investigate the pharmacodynamic efficacy and safety of eculizumab (complement C5 antibody) in patients with aSAH. Methods A randomized, controlled, open-label, phase II clinical trial with blinded outcome assessment. Eculizumab (1200 mg) is administered intravenously <12 hours, on day 3 and on day 7 after ictus. Patients in the intervention group receive prophylactic antibiotics for 4 weeks, and those with a central line or an external ventricular shunt and a positive fungal or yeast culture also receive prophylactic antifungal therapy for 4 weeks. The primary outcome is C5a concentration in cerebrospinal fluid (CSF) on day 3 after ictus. Secondary outcomes include the occurrence of adverse events, inflammatory parameters in blood and CSF, cerebral infarction on magnetic resonance imaging, and clinical- and cognitive outcomes. We aim to evaluate 26 patients with CSF assessments, 13 in the intervention group and 13 in the comparator group. To compensate for early case-fatality and inability to obtain CSF, we will include 20 patients per group. Discussion The CLASH trial is the first trial to investigate the pharmacodynamic efficacy and safety of eculizumab in the early phase after aSAH. Trial registration Netherlands Trial Register: NTR6752, https://www.trialregister.nl/trial/6579. Registered on 27 October 2017. European Clinical Trials Database: EudraCT 2017-004307-51.

scholarly journals CompLement C5 Antibodies for decreasing brain injury after aneurysmal Subarachnoid Hemorrhage (CLASH): study protocol for a randomized controlled phase II clinical trial

2020 ◽  
Author(s):  
Inez Koopman ◽  
Gabriel J.E. Rinkel ◽  
Mervyn D.I. Vergouwen
Keyword(s):  
Clinical Trial ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Phase Ii ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Intervention Group ◽  
Case Fatality ◽  
Phase Ii Clinical Trial ◽  
Efficacy And Safety ◽  
Randomized Controlled

Abstract BackgroundThe inflammatory response after aneurysmal subarachnoid hemorrhage (aSAH) has been associated with early brain injury, delayed cerebral ischemia, poor functional outcome, and case-fatality. In experimental SAH studies, complement C5 antibodies administered shortly after SAH reduce brain injury with approximately 40%. Complement component C5 may be a new therapeutic target to reduce brain injury and hereby improve outcome after aSAH. We aim to investigate the pharmacodynamic efficacy and safety of eculizumab (complement C5 antibody) in patients with aSAH.MethodsA randomized, controlled, open-label, phase II clinical trial with blinded outcome assessment. Eculizumab (1200 mg) is administered intravenously <12 hours, on day 3 and on day 7 after ictus. Patients in the intervention group receive prophylactic antibiotics for 4 weeks, and those with a central line or an external ventricular shunt and a positive fungal or yeast culture also receive prophylactic antifungal therapy for 4 weeks. The primary outcome is C5a concentration in cerebrospinal fluid (CSF) on day 3 after ictus. Secondary outcomes include the occurrence of adverse events, inflammatory parameters in blood and CSF, cerebral infarction on magnetic resonance imaging, and clinical- and cognitive outcomes. We aim to evaluate 26 patients with CSF assessments, 13 in the intervention group and 13 in the control group. To compensate for early case fatality and inability to obtain CSF, we will include 20 patients per group.DiscussionThe CLASH trial is the first trial to investigate the pharmacodynamic efficacy and safety of eculizumab in the early phase after aSAH.Trial registrationNetherlands Trial Register: NTR6752, https://www.trialregister.nl/trial/6579. Registered on 27 October 2017. European Clinical Trials Database: EudraCT 2017-004307-51.

Efficacy and safety of liposomal mitoxantrone (Lipo-MIT) in advanced breast cancer (ABC): A randomized, open label, active-controlled, single-center, phase II clinical trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1093-1093
Author(s):  
Leiping Wang ◽  
Yannan Zhao ◽  
Ting Li ◽  
Jun Cao ◽  
Yiqun Du ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Lower Incidence ◽  
Troponin T ◽  
Objective Response ◽  
Phase Ii Clinical Trial ◽  
Efficacy And Safety ◽  
Single Center ◽  
Open Label

1093 Background: Anthracyclines are associated with cardiotoxicity and myelosuppression in breast cancer (BC) patients. A new drug delivery system, liposomal preparation has shown higher anti-cancer effect and lower toxicity due to modified drug release and particle shape. This trial aimed to evaluate the efficacy and safety of Lipo-MIT in ABC. Methods: This is a randomized, open label, active-controlled, single-center, phase II clinical trial. Eligible patients were randomized in a ratio of 1:1 to receive Lipo-MIT or mitoxantrone hydrochloride injection (MIT) intravenously. The dosage was 20 mg/m2 for Lipo-MIT and 14 mg/m2 for MIT, once every four weeks (i.e., one treatment cycle). The primary endpoint was objective response rate(ORR). The secondary endpoints were progression free survival (PFS) and safety. Results: From Oct 2015 through Jul 2017, 60 patients were randomized to Lipo-MIT group (n = 30) or MIT group (n = 30). The Median (Q1,Q3) age was 56.0 (41.0,62.0) years in Lipo-MIT group and 54.5 (44.0,62.0) years in MIT group. Nineteen patients in Lipo-MIT group and 23 in MIT group received < 4 cycles of treatment, 11 patients in Lipo-MIT group and 7 in MIT group were treated for 4 or more cycles. When Lipo-MIT group was compared with MIT group, ORR was 13.3% (4/30) and 6.7% (2/30), disease control rate (PR+SD) was 50% (15/30) and 30% (9/30), median PFS was 2.30 (95% CI: 1.74-3.91) and 1.86 (95% CI: 1.74-2.40) months ( P> 0.05). Lipo-MIT showed significantly lower incidence of all-grade white blood cell decreased (86.7% vs 96.7%), neutrophil count decreased (80.0% vs 96.7%), conjugated bilirubin increased (53.3% vs 56.7%), aspartate aminotransferase increased (40.0% vs 53.3%), and troponin T increased (3.3% vs 36.7%) than MIT, but higher incidence of anemia (76.7% vs 46.7%), skin hyperpigmentation (66.7% vs 3.3%), and platelet count decreased (56.7% vs 53.3%) than MIT. Conclusions: Lipo-MIT provided numerically better ORR, DCR, and PFS than MIT in ABC. Lower incidence of troponin T increased might suggest lower cardiotoxicity of Lipo-MIT. It is worthwhile to further explore the clinical utility of Lipo-MIT in ABC. Clinical trial information: NCT02596373 .

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