protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
|---|---|---|---|---|
NCT03085758 | 4.3 | Endpoints for Primary Objective (Safety and Tolerability) | 4.3 Endpoints for Primary Objective (Safety and Tolerability) The endpoints for the primary objective are to determine over the 90 days study period: - Mortality - Interruption of infusion - Severity and frequency of treatment-emergent adverse events | [] |
NCT03085758 | 4.4 | Endpoints for Secondary Objective (Efficacy) | 4.4 Endpoints for Secondary Objective (Efficacy) The primary efficacy endpoint of this study is the • Sepsis Support Index (SSI) defined as: days with organ support or dead within 14 day follow up More precisely: In the time frame of 14 day follow-up, each day on support with vasopressor, and/or mechanical ventilation ... | [] |
NCT03085758 | 4.5 | Endpoints for Pharmacokinetics | 4.5 Endpoints for Pharmacokinetics In sub-study (with 80 patients only) to determine key PK parameters, including: - peak plasma concentrations (Cmax) - systemic exposure (AUC) - volume of distribution (V) - systemic clearance (CL) - elimination half-life (t½)  EudraCT-No: 2016-003883-38 | [] |
NCT03085758 | 5 | INVESTIGATIONAL PLAN | 5. INVESTIGATIONAL PLAN | [] |
NCT03085758 | 5.1 | Study Design | 5.1 Study Design This study is designed to evaluate the potential of ADRECIZUMAB as targeted therapy in preselected patient using the biomarker ADM with regard to safety and tolerability, PK and efficacy. Therefore, it is intended to enroll patients with "early" septic shock (start of vasopressor therapy 70 pg/ml. For ... | [] |
NCT03085758 | 5.2 | Study Population | 5.2 Study Population | [] |
NCT03085758 | 5.2.1 | Selection of Study Population | 5.2.1 Selection of Study Population In this phase II study up to 300 adult male and female patients with "early" septic shock and a bio-ADM concentration at inclusion of > 70 pg/mL will participate. To qualify for randomization and treatment with the study medication, patients must meet all inclusion criteria and none ... | [] |
NCT03085758 | 5.2.2 | Inclusion Criteria | 5.2.2 Inclusion Criteria To participate in the study, patient must meet all of the following inclusion criteria: - 1. Written informed consent by patient or legally designated representative (according to country – specific regulations) - 2. Male and female patients, age ≥ 18 years - 3. Body weight 50 kg 120 kg - 4. Bi... | [
"Definition:"
] |
NCT03085758 | 5.2.3 | Exclusion Criteria | 5.2.3 Exclusion Criteria A patient who meets any of the following criteria must be excluded from the study: - 1. Moribund - 2. Pre-existing unstable condition (e.g. a recent cerebral hemorrhage or infarct, a recent acute unstable myocardial infarction (all 30% of body surface - 13. Plasmapheresis - 14. Breastfeeding wo... | [] |
NCT03085758 | 5.3 | Patient Numbering | 5.3 Patient Numbering Inclusion- and exclusion criteria from patients admitted to the ICU will be verified by the investigator to identify potential patients to be enrolled into the study. After availability of written informed consent by patient or legally designated representative (or other accepted procedure accordi... | [] |
NCT03085758 | 5.4 | Screen Failure Patients | 5.4 Screen Failure Patients Patients who sign the informed consent form but fail to meet one or more of the eligibility criteria, or who decline study participation before receiving IMP, will be defined as screen failures. For those patients the investigator will be asked to contact the patient on day 14 for calculatio... | [] |
NCT03085758 | 5.5 | Discontinuation of Individual Subjects | 5.5 Discontinuation of Individual Subjects Participation in this clinical study is strictly voluntary and any subject may withdraw from the study at any time without providing an explanation. This will not affect his/her right for future medical care. In the event that a patient withdraws from the study, the investigat... | [] |
NCT03085758 | 5.6 | Stopping of Clinical Trial | 5.6 Stopping of Clinical Trial All safety signals including suspected unexpected serious adverse reaction (SUSAR) and SAEs will be reviewed on a continuous basis by the Data and Safety Monitoring Board (DSMB) (see section 12.5). The stopping rules defined below apply to any treatment-related AE and clinical laboratory ... | [] |
NCT03085758 | 5.7 | Concomitant Treatment | 5.7 Concomitant Treatment Standard medical treatment(s), including all therapies and medications, prescriptions and overthe-counter, being taken by the patient upon entry in the study, maintained throughout the study including any medication to treat AEs or SAEs will be collected. Any changes in concomitant medication ... | [] |
NCT03085758 | 5.8 | Cornerstone Medication - Permitted Concomitant Medication | 5.8 Cornerstone Medication - Permitted Concomitant Medication The main therapy administered according to the international guidelines for treatment of patients with septic shock (Surviving Sepsis Campaign), e.g. enteral / parenteral nutrition, antimicrobiotic therapy (drug, dose, duration), insulin, blood transfusion s... | [] |
NCT03085758 | 5.9 | Vasopressor Therapy | 5.9 Vasopressor Therapy Vasopressors are provided for patients with septic shock who do not respond to fluid resuscitation. Use of vasopressors (dopamine, dobutamine, phenylephrine) in combination with catecholamine (adrenaline, noradrenaline\) will be recorded from admission to ICU at time point of diagnosis of septic... | [] |
NCT03085758 | 5.10 | Lost to Follow-up | 5.10 Lost to Follow-up For patients whose status is unclear because they fail to appear for the follow-up visit on day 28 and fail to have the phone call on day 90 without stating an intention to withdraw, the investigator should show "due diligence" by contacting the subject, family or family physician as agreed in th... | [] |
NCT03085758 | 6 | INVESTIGATONAL TREATMENTS | 6. INVESTIGATONAL TREATMENTS | [] |
NCT03085758 | 6.1 | Investigational Medicinal Product (IMP) | 6.1 Investigational Medicinal Product (IMP) ADRECIZUMAB (HAM8101) is a humanized IgG1 monoclonal antibody (mAb) directed against the N-terminus of adrenomedulling (ADM) and intended for the treatment of sever sepsis and septic shock. The antibody was generated by complementarity determining region (CDR) grafting a muri... | [] |
NCT03085758 | 6.2 | Packaging, Labeling and Shipment | 6.2 Packaging, Labeling and Shipment ADRECIZUMAB 200 mg solution for infusion and ADRECIZUMAB placebo are in clear Type I glass vials, size 10R, sealed with fluoropolymer coated bromobutyl rubber stoppers and tearoff plain aluminum cover seals. Clinical supplies are provided in boxes containing 8 vials respectively. In... | [] |
NCT03085758 | 6.3 | Handling, Storage and Preparation | 6.3 Handling, Storage and Preparation The IMP kits must be stored at temperature between 2°C – 8 °C, protected from light under temperature controlled and restricted access conditions either in the local pharmacy or at the ICU. Any temperature deviation (temperature below +2°C and/or above +8°C) must be reported to the... | [] |
NCT03085758 | 6.4 | Accountability | 6.4 Accountability In agreement with the sponsor, the PI will designate a responsible person for receipt, storage and preparation of the study medication. Regular study drug reconciliation will be performed throughout the study to document drug assigned, drug administered, and drug remaining, or drug inadvertently dama... | [] |
NCT03085758 | 6.5 | Treatment Assignment | 6.5 Treatment Assignment | [] |
NCT03085758 | 6.5.1 | Randomization Procedures | 6.5.1 Randomization Procedures In order to ensure the appropriate number of patients to be enrolled on identifying a potential study patient the investigator is required to complete a site authorization worksheet for confirming patient eligibility by the central Clinical Coordination Center (CCC). When appropriate inve... | [] |
NCT03085758 | 6.5.2 | Maintenance of the Randomization Code | 6.5.2 Maintenance of the Randomization Code This study will be performed in a double-blind fashion. The Investigator and site staff, patients, monitors, Sponsor and CRO staff will remain blinded to the treatment assignment until study closure. The investigational drug and its matching placebo are indistinguishable and ... | [] |
NCT03085758 | 6.5.3 | Emergency Unblinding | 6.5.3 Emergency Unblinding Under normal circumstances, the blinding should not be broken. The blinding should be broken only if specific emergency treatment would be indicated by knowing the treatment status of the patient. Whenever a code is broken, the person breaking the code must record the time, date and reason as... | [] |
NCT03085758 | 6.5.4 | Routine Unblinding | 6.5.4 Routine Unblinding After completion of the study, locking of the clinical database, and performance of a blinded data review, a routine unblinding will be authorized by the Sponsor.  EudraCT-No: 2016-003883-38 | [] |
NCT03085758 | 7 | STUDY CONDUCT | 7. STUDY CONDUCT | [] |
NCT03085758 | 7.1 | Standards of Study Conduct | 7.1 Standards of Study Conduct This study will be conducted in compliance with applicable regulatory requirements, in particular the EU Clinical Trials Directive and the Declaration of Helsinki. It will be conducted strictly following the study protocol and in compliance with the revised ICH guidance E6, the EU-GCP dir... | [] |
NCT03085758 | 7.2 | Informed Consent | 7.2 Informed Consent | [] |
NCT03085758 | 7.2.1 | Patients Able to Provide Consent Personally | 7.2.1 Patients Able to Provide Consent Personally Prior to any study-related activity, any patient to be included in this study must give informed consent in accordance with the EU Clinical Trial Directive, the Declaration of Helsinki and with ICH-GCP requirements. The responsibility for obtaining informed consent rema... | [] |
NCT03085758 | 7.2.2 | Patients Unable to Provide Consent Personally | 7.2.2 Patients Unable to Provide Consent Personally For patients unable to give consent due to the emergency nature of the patient's condition the investigator will provide sufficient information about the study to the legally designated representative of the patient, designated according to the applicable national law... | [] |
NCT03085758 | 7.2.3 | Screen Failure Patients | 7.2.3 Screen Failure Patients In case the patient was unable to provide consent personally and information about the study was provided to the the legally designated representative of the patient and informed consent was obtained from the legally designated representative of the patient afterwards, investigator should ... | [] |
NCT03085758 | 7.3 | Protocol Amendments | 7.3 Protocol Amendments Changes to the protocol during the study will be documented as amendments. The amended protocol will be signed by the relevant personnel at ADRENOMED AG und by the investigator. Depending on the content of the amendment and local legal requirements, the amendment will be submitted to the relevan... | [] |
NCT03085758 | 7.4 | Study Visits and Procedures | 7.4 Study Visits and Procedures Study procedures are scheduled for screening, administration of study medication and for assessment of the safety and tolerability of the investigational treatment, as well as until end of study as outlined in the flow-charts (Figure 1, Figure 2 and Figure 3). The procedures on particula... | [] |
NCT03085758 | 7.4.1 | Pre-Treatment: Screening | 7.4.1 Pre-Treatment: Screening Before starting any screening procedure, patient or legally designated representative must provide written informed consent as described in protocol section 7.2.1 and 7.2.2. The investigator will keep a log of all screened and randomized patients. For patients who were not entered into th... | [] |
NCT03085758 | 7.4.2 | Eligibility Confirmation: | 7.4.2 Eligibility Confirmation: For patients who meet all inclusion criteria and do not meet any of the exclusion criteria a site authorization worksheet will be completed and forwarded to the central CCC in Brussels for confirmation of patients' eligibility. | [] |
NCT03085758 | 7.4.3 | Day 1: Start of Treatment | 7.4.3 Day 1: Start of Treatment Permission for randomization for the central CCC granted by receipt of the authorization number. The patient will then be randomized to one of the two treatment arms (A or B) or to the control group (placebo) and the following activities and assessments will be performed: - Prior to IMP ... | [
"Day 2 – Day 28 (or discharge, whatever comes first)"
] |
NCT03085758 | 7.4.4 | Follow-up Period | 7.4.4 Follow-up Period
Day 28 (+/- 3 days) The following activities and assessments will be performed for all patients already discharged from ICU prior to day 28: - Recording of vital signs - Blood sampling for laboratory examinations: BUN or urea, sodium, creatinine, total bilirubin,platelet count, hemoglobin, hemat... | [
"Day 28 (+/- 3 days)",
"Day 90 (+/-3 days)"
] |
NCT03085758 | 7.4.5 | Screen Failure Patients | 7.4.5 Screen Failure Patients Patients who did not get permission to be randomized by the central CCC in Brussels after completion of the screening procedures (see 7.4.1) or who decline study participation before receiving IMP will be defined as screen failures. Additional informed consent from the patient or the legal... | [
"Screening – day 14 (or discharge)",
"Follow-up Period Day 28 and Day 90"
] |
NCT03085758 | 7.5 | Premature Discontinuation | 7.5 Premature Discontinuation All patient have the right to withdraw formal consent without prejudice at any time during the study. If a patient withdraws formal consent, the investigator should make a reasonable effort to determine the cause for withdrawal of consent. For these patients, as well as all other patients ... | [] |
NCT03085758 | 7.6 | Visit Window | 7.6 Visit Window The study flow chart (see Figure 2.1) must be followed. However, under special conditions, e.g. holidays, weekends, etc. a window of +/- 3 days is allowable for the day 28 follow-up visit as well as for the follow-up phone call on day 90. These visit windows are not applicable for day 1 through day 28 ... | [] |
NCT03085758 | 8 | STUDY PROCEDURES | 8. STUDY PROCEDURES | [] |
NCT03085758 | 8.1 | Demography | 8.1 Demography Demographic data are to be collected at screening and will include age, gender, Ethnic origin as well as body weight and height. | [] |
NCT03085758 | 8.2 | Medical History | 8.2 Medical History In addition to the diagnosis of early septic shock all ongoing conditions and relevant medical history and co-morbidities present or treated within the last year (cardiovascular and noncardiovascular) and concomitant illnesses present at inclusion need to be documented. Whenever possible, diagnosis ... | [] |
NCT03085758 | 8.3 | Physical Examination | 8.3 Physical Examination Physical examination including general appearance will be assessed at inclusion into the study. Physical examination will include the following body systems: - Mouth, ear, nose, throat - Thyroid and neck - Lymph nodes and spleen - Respiratory system - Cardiovascular system including blood press... | [] |
NCT03085758 | 8.4 | Vital Signs and Body Temperature | 8.4 Vital Signs and Body Temperature Vital signs (blood pressure, heart rate, MAP, respiratory rate and oral or tympanic temperature) will be collected at screening and daily from day 1 to day 28 or discharge as well as on the follow-up visit day 28. Vital signs must be assessed as min/max values within 24 hours except... | [] |
NCT03085758 | 8.5 | Glasgow Coma Scale | 8.5 Glasgow Coma Scale GCS will be used for daily assessment of impairment of conscious level in response to define stimuli after confirmation of eligibility on day 1 shortly before IMP administration. Lowest (worst) value of GCS will be recorded daily from day 2 to day 28 or discharge. Observations on patient's curren... | [] |
NCT03085758 | 8.6 | Fluid Balance | 8.6 Fluid Balance Daily fluid intake will be calculated as the sum of all intravenous and oral fluids. The daily fluid output will be calculated as the sum of the volume of urine output, ultrafiltration fluid, drain fluid, and estimated gastrointestinal losses (including stools only in the presence of profound diarrhea... | [] |
NCT03085758 | 8.7 | 12-lead ECG | 8.7 12-lead ECG A standard 12-lead ECG will be recorded at screening in supine or semi-supine position, if not already done at any time after diagnosis of septic shock. The ECG device will compute overall rhythm analysis, heart rate, P wave, PQ interval, QRS duration, QT and QTc intervals. The QT interval will be corre... | [] |
NCT03085758 | 8.8 | Local Laboratory Assessments | 8.8 Local Laboratory Assessments Laboratory examinations are done locally as part of routine clinical care during stay in ICU and at the day 28 follow-up visit. In order to verify the patient's eligibility for the study during screening, lab values can be used which have already been analysed for clinical routine (e.g.... | [] |
NCT03085758 | 8.8.1 | Day 2 through day 7 or discharge (whatever comes first) | 8.8.1 Day 2 through day 7 or discharge (whatever comes first) Daily blood collection (taken at the morning routine) for assessment of safety laboratory markers (hematology – blood sample up to 2 mL blood, biochemistry – blood sample approximately 2,5 mL) will be performed. The following parameters will be assessed: BUN... | [] |
NCT03085758 | 8.8.2 | Day 8 through Day 27 or discharge (whatever comes first): | 8.8.2 Day 8 through Day 27 or discharge (whatever comes first): The following parameters will be measured daily: PaO2/FiO2 (if arterial line in place), arterial pH and creatinine. Total bilirubin, platelet count and blood lactate concentration will be measured every other day.  EudraCT-No: 2016-... | [] |
NCT03085758 | 8.8.3 | Follow-up Day 28: | 8.8.3 Follow-up Day 28: For assessment of safety laboratory markers a blood sample (approximately 4,5 mL) will be collected for analysis of BUN (calculated) or urea, sodium, creatinine, total bilirubin, blood lactate concentration, platelet count, hemoglobin, hematocrit, white blood count. | [] |
NCT03085758 | 8.8.4 | Pregnancy test | 8.8.4 Pregnancy test Pregnancy test (urine or serum ß-HCG ) will be performed in all women to assure that no pregnant women is included in the study. Female patients who are not of childbearing potential due to being postmenopausal (2 years without menstruation) or surgically sterilised (oophorectomy, hysterectomy and/... | [] |
NCT03085758 | 8.9 | Blood Sampling for bio-ADM and Biomarker | 8.9 Blood Sampling for bio-ADM and Biomarker | [] |
NCT03085758 | 8.9.1 | Blood Sampling for measurement of bio-ADM ( screening) | 8.9.1 Blood Sampling for measurement of bio-ADM ( screening) For measurement of bio-ADM concentation a 5 mL EDTA plasma sample will be collected (derived from EDTA blood). For measurement of bioactive Adrenomedullin in human EDTAplasma the sphingotest® bio-ADMCDx, a immuno luminometric assay (ILMA) will be used. ADM me... | [] |
NCT03085758 | 8.9.2 | Blood Sampling for Biomarker for central laboratory | 8.9.2 Blood Sampling for Biomarker for central laboratory Blood samples for determination of the biomarkers MR-pro-ADM, inflammatory biomarkers PCT, IL-6 and penKid will be taken prior to start of IMP infusion (day 1) and within the time frame of 24 hours +/- 10 hours after end of IMP infusion (day 2). Further timepoin... | [] |
NCT03085758 | 8.10 | Organ Dysfunction Characterized by SOFA Score | 8.10 Organ Dysfunction Characterized by SOFA Score It is intended to calculate the SOFA score on each day the patient remains in the ICU from day 1 (shortly before IMP administration) and daily from day 2 through day 28 or discharge (whatever comes first) as an expression for organ dysfunction. Therefore, kidney functi... | [] |
NCT03085758 | 8.11 | Pharmacokinetic Analysis - Substudy | 8.11 Pharmacokinetic Analysis - Substudy Pharmacokinetic (PK) samples from 80 patients will be collected at designated sites participating in the PK substudy. Plasma samples for PK analysis from 80 patients receiving either ADRECIZUMAB 2 mg/kg body weight (treatment arm A) or ADRECIZUMAB 4 mg/kg body weight (treatment ... | [] |
NCT03085758 | 8.12 | Contraception, Pregnancy, Breastfeeding | 8.12 Contraception, Pregnancy, Breastfeeding | [] |
NCT03085758 | 8.12.1 | Contraception | 8.12.1 Contraception Female patients who are not of childbearing potential due to being postmenopausal (2 year without menstruations) or surgically sterilized (oophorectomy, hysterectomy and/or tubal ligation) do not need to use contraception to be eligible for the study. All other female patients are considered to be ... | [] |
NCT03085758 | 8.12.2 | Pregnancy | 8.12.2 Pregnancy The site will contact the patient at least monthly and document the patient's status until the pregnancy has been completed or terminated. The outcome of the pregnancy will be reported to the safety department of the sponsor without delay and within 24 hours if the outcome is a serious adverse experien... | [] |
NCT03085758 | 8.12.3 | Breatfeeding Women | 8.12.3 Breatfeeding Women It is unknown whether ADRECIZUMAB is excreted in human milk. Because of the potential for serious adverse reactions in the nursing infant, patients who are breast-feeding are not eligible for randomization.  EudraCT-No: 2016-003883-38 | [] |
NCT03085758 | 8.13 | Patient Reported Outcomes | 8.13 Patient Reported Outcomes Euro-QoL – 5 Quality of Life Short Form will be completed at the day of discharge from ICU (day 2 to day 28, whatever comes first), and on follow-up day 28. Patients will be called from the investigator's site on follow-up day 90 after end of infusion of study medication for completion of... | [] |
NCT03085758 | 8.14 | Echocardiography (optional) | 8.14 Echocardiography (optional) If transthoracic or transeosophageal echocardiography is performed at screening , left ventricle end-diastolic diameter, right ventricular end-diastolic diameter, inferior vena cava diameter (and respiratory variation) and left ventricular ejection fraction will be recorded. Each origin... | [] |
NCT03085758 | 9 | PHARMACOVIGILANCE | 9. PHARMACOVIGILANCE | [] |
NCT03085758 | 9.1 | Definitions | 9.1 Definitions | [] |
NCT03085758 | 9.1.1 | Adverse Event (AE) | 9.1.1 Adverse Event (AE) An AE is defined as any untoward medical occurrence in a patient or clinical study patient administered a product and which does not necessarily have a causal relation-ship with this treatment. Examples of AEs include one of the following or a combination of two or more of these factors: - Any ... | [] |
NCT03085758 | 9.1.2 | Serious Adverse Event (SAE) | 9.1.2 Serious Adverse Event (SAE) An SAE is any untoward medical occurrence that at any dose (including overdose): • Results in death  EudraCT-No: 2016-003883-38
• Is life-threatening "Life-threatening" means that the patient was at immediate risk of death at the time of the SAE; it does not re... | [
"• Is life-threatening",
"• Misuse and overdose:"
] |
NCT03085758 | 9.1.3 | Recommendations to Treat Overdosing and Intoxication with the Study Medication | 9.1.3 Recommendations to Treat Overdosing and Intoxication with the Study Medication No drug-specific antidote is available. Other emergencies will be treated symptomatically according to standard medical practice. | [] |
NCT03085758 | 9.1.4 | Investigational Product Complaints | 9.1.4 Investigational Product Complaints Pharmaceutical technical complaints associated with the investigational product must be reported to the sponsor immediately: > ADRENOMED AG Neuendorfstr. 15a 16761 Hennigsdorf Germany The same reporting timelines as for serious adverse events apply. | [] |
NCT03085758 | 9.2 | Period of Observation | 9.2 Period of Observation For the purpose of this study, the period of observation for collection of AEs extends from screening until 90 days after end of IMP administration. If the investigator detects an AE in a study patient after the end of the period of observation, and considers the event possibly related to prio... | [] |
NCT03085758 | 9.3 | Documentation and Reporting of Adverse Events | 9.3 Documentation and Reporting of Adverse Events | [] |
NCT03085758 | 9.3.1 | Documentation and Reporting of Adverse Events by Investigator | 9.3.1 Documentation and Reporting of Adverse Events by Investigator The investigator must document all AEs that occur during the observation period set in this protocol in the eCRF. Additional instructions may be provided in the Investigator Site File and in the eCRFs itself. The following approach will be taken for do... | [] |
NCT03085758 | 9.3.2 | Assessment of Severity | 9.3.2 Assessment of Severity The investigator will also provide an assessment of the severity of the event and causal relationship between the event and the investigational product or trial procedures. The basis of assessing severity and causality is described as: - Grade 1 mild event: Causing no limitations of usual a... | [] |
NCT03085758 | 9.3.3 | Assessment of Causality | 9.3.3 Assessment of Causality The investigator will use medical judgment to determine whether there is evidence for a causal relationship, including all relevant factors such as temporal course and latency, results from dechallenge or re-challenge, pattern of the reaction, known pharmacological properties of the produc... | [] |
NCT03085758 | 9.3.4 | Follow-up of Missing Information | 9.3.4 Follow-up of Missing Information Information not available at the time of the initial SAE report (e.g., an end date for the SAE or laboratory values received after the report) must be documented on a "Serious Adverse Event" form, with the box "Follow-up" checked under "Report type". All subjects who have AEs, whe... | [] |
NCT03085758 | 9.3.5 | Determination of Expectedness, Reference Safety Information | 9.3.5 Determination of Expectedness, Reference Safety Information Expectedness will be determined by the sponsor according to the designated Reference Safety Information. Any updates or substantial amendments will be considered accordingly. The Reference Safety Information for the investigational medicinal product will... | [
"Unexpected:"
] |
NCT03085758 | 9.3.6 | Expedited Reporting of Adverse Events / SUSAR Reporting | 9.3.6 Expedited Reporting of Adverse Events / SUSAR Reporting All AEs and SAEs will be classified according to severity and causality.The sponsor will report all those serious and unexpected AEs, which are judged by either the investigator or the sponsor as having a reasonable suspected causal relationship i.e. SUSAR, ... | [
"Unblinding:",
"Development Safety Update Reports:"
] |
NCT03085758 | 9.4 | Follow-up of Adverse Events | 9.4 Follow-up of Adverse Events All AEs will be followed until they have abated, or until a stable situation has been reached. Depending on the event, follow-up may require additional tests or medical procedures as indicated, and/or referral to the general physician or a medical specialist. The Investigator is expected... | [] |
NCT03085758 | 10 | STATISTICAL CONSIDERATIONS | 10. STATISTICAL CONSIDERATIONS A full statistical analysis plan will be drawn up before the trial database is locked and analyzed. Prior to performing any statistical tests or fitting statistical models, an exploratory analysis of the baseline variables and outcome measures will be completed. The level and pattern of m... | [] |
NCT03085758 | 10.1 | Demographic and Other Baseline Characteristics | 10.1 Demographic and Other Baseline Characteristics Demographic characteristics will be listed and summarized. | [] |
NCT03085758 | 10.2 | Statistical Methods for Safety Parameters | 10.2 Statistical Methods for Safety Parameters All safety and tolerability assessment will be based on the safety analysis set, which is defined as all patients who have received study medication. | [] |
NCT03085758 | 10.3 | Handling of Withdrawals, Protocol Deviations and Missing Values | 10.3 Handling of Withdrawals, Protocol Deviations and Missing Values Data from subjects who prematurely terminate the study will be used to the maximum extent possible. Missing data in the primary efficacy endpoint will be dealt with using sensitivity analysis. Details will be outlined in the statistical analysis plan.... | [] |
NCT03085758 | 10.4 | Safety Analysis | 10.4 Safety Analysis Safety monitoring will begin at the time the Informed Consent Form (ICF) is signed and will continue for 90 days after short-term infusion of study medication. All AEs will be listed. The number and percent of patients experiencing 1 or more AEs will be summarized by treatment arm / control group, ... | [] |
NCT03085758 | 10.5 | Efficacy Analysis | 10.5 Efficacy Analysis The primary analysis for efficacy will be based on combining both ADRECIZUMAB doses and comparing the treated groups versus the placebo group. A second-line analysis will compare the two doses for differences in efficacy. For the primary efficacy endpoints, a first analysis will determine whether... | [] |
NCT03085758 | 10.5.1 | Sepsis Support Index (SSI) and Penalized Sepsis Support Index (pSSI) | 10.5.1 Sepsis Support Index (SSI) and Penalized Sepsis Support Index (pSSI) SSI as primary efficacy endpoint is defined as days with organ support or dead within 14 day follow up. Organ support days are defined as days with vasopressor, mechanical ventilation or renal replacement therapy (defined as renal SOFA = 4 due ... | [] |
NCT03085758 | 10.5.2 | All-cause Mortality at Follow-up Day 28 and Day 90 | 10.5.2 All-cause Mortality at Follow-up Day 28 and Day 90 All-cause mortality will be evaluated using Kaplan-Meier plots comparing treatment vs. placebo (log-rank test) and Cox regression modelling including covariates to adjust for potential confounders, e.g. severity, age and others. | [] |
NCT03085758 | 10.5.3 | SOFA Score | 10.5.3 SOFA Score The SOFA score will be evaluated daily for all patients over the entire stay on ICU (as long as the arterial line is in place) until day 28 or discharge (whatever comes first). In the calculation of the score, the worst values for each parameter in the 24 hours period will be used. In sedated patients... | [] |
NCT03085758 | 10.6 | Sample Size Determination / Power Analysis for Primary Efficacy Endpoint (SSI within 14 days) | 10.6 Sample Size Determination / Power Analysis for Primary Efficacy Endpoint (SSI within 14 days) Power simulations are based on using real patient data on the combined endpoint from the ALBIOS study, and underlying assumptions were re-evaluated using results from the AdrenOSS observational study.. - Details of the si... | [
"Power Analysis Assumptions",
"Interim Analysis with Futility Stop",
"Power Considerations Summary"
] |
NCT03085758 | 10.7 | Statistical Methods for Pharmacokinetic Parameters | 10.7 Statistical Methods for Pharmacokinetic Parameters The analysis plan for PK assessment for the study will be part of the SAP. PK of ADRECIZUMAB profile is studied after single administration of ADRECIZUMAB 2 mg/kg and 4 mg/kg in order to determine key PK parameters, including peak plasma concentrations (Cmax), sys... | [] |
NCT03085758 | 10.8 | Analysis of Observational Data and Exploratory Analysis | 10.8 Analysis of Observational Data and Exploratory Analysis Several post-hoc analyses using all patients included in the study are planned, such as analyzing the association between 28 day mortality rate/ vasopressor use/ ventilation and bio-ADM. Exploratory post-hoc analysis of efficacy endpoints in patient subgroups... | [] |
NCT03085758 | 11 | DATA MANAGEMENT and DATA HANDLING | 11. DATA MANAGEMENT and DATA HANDLING | [] |
NCT03085758 | 11.1 | Data Management | 11.1 Data Management All data management activities will be done according to ICH-GCP as required by regulatory agencies. Responsibility for data management lies with the designated CRO following their internal standard operating procedures (SOPs). The designated CRO will be responsible for the activities associated wi... | [] |
NCT03085758 | 11.2 | Data Handling and Recording of Data | 11.2 Data Handling and Recording of Data All data collected during the study have to be recorded in an electronic CRF (eCRF) which is provided in an internet portal. This eCRF will be designed by M.A.R.C.O. GmbH & Co. KG (M.A.R.C.O) in the Amedon system. The Amedon system has been validated by Amedon GmbH for use in cl... | [] |
NCT03085758 | 11.3 | Source Data | 11.3 Source Data Source data is all information, original records of clinical findings, observations, or other activities in a clinical study necessary for the reconstruction and evaluation of the study. Source data are contained in source documents. Examples of these original documents, and data records include: hospi... | [] |
NCT03085758 | 12 | ETHICAL CONSIDERATIONS | 12. ETHICAL CONSIDERATIONS | [] |
NCT03085758 | 12.1 | Good Clinical Practice | 12.1 Good Clinical Practice The investigator will ensure that this clinical study is conducted in accordance with the principles of the Good Clinical Practices (GCP), ICH Guidelines, and the Declaration of Helsinki and with the laws and regulations of the country in which the research is conducted, whichever affords th... | [] |
NCT03085758 | 12.2 | Independent Ethic Committees (IEC) and Competent Authorities (CAs) | 12.2 Independent Ethic Committees (IEC) and Competent Authorities (CAs) The study will only start after approval of the study protocol and all relevant documentation by the IRB/IEC and CA of the participating countries. In addition, all local national legal requirements for the conduct of a clinical study have to be fo... | [] |
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