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| ID | Type | Description | Link |
|---|---|---|---|
| C4791011 | Other Identifier | Alias Study Number |
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This is a multicenter, open-label, single arm study to evaluate the efficacy and safety of APX001 for the treatment of candidemia and/or invasive candidiasis caused by C. auris in patients aged 18 years and over with limited antifungal treatment options.
This is a multicenter, open-label, non-comparative, single arm study to evaluate the efficacy and safety of APX001 for the treatment of candidemia and/or invasive candidiasis caused by C. auris in patients aged 18 years and over with limited antifungal treatment options. The Study Drug Treatment Period will be up to a maximum of 42 days (inclusive of the loading dose [Study Day 1]). There will be a Follow up Period of 4 weeks (+4 days) after EOST. The total duration of participation in the study is up to approximately 10.5 weeks (inclusive of the Screening Period [168 hours prior to Baseline]).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| APX001 | Experimental | APX001 IV or oral for up to 42 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| APX001 | Drug | Day 1: APX001 1000 mg IV BID over a 3-hour infusion Days 2-3: APX001 600 mg IV QD over a 3-hour infusion Days 4 - 42: APX001 600 mg IV QD over a 3-hour infusion or APX001 800 mg QD oral. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Treatment Success at End of Study Treatment (EOST) as Determined by Data Review Committee (DRC) | Treatment success was defined as meeting all of the following criteria: 1) Two consecutive blood cultures negative for Candida species, and/or for participants with a deep-seated site of infection, at least 1 negative tissue culture or aspirate/fluid culture. For participants with a deep-seated site of infection involving visceral organs from which a tissue culture was not obtainable, resolution of the attributable clinical signs of infection recorded at Baseline, and as applicable, radiological improvement associated with the site of infection. 2) Alive at EOST and 3) No concomitant use of any other systemic antifungal therapies through EOST. | EOST: any day from Day 1 up to maximum of Day 42 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to First Negative Blood Culture | Time to first negative blood culture was defined as the number of days from date of first dose of study drug to the date of first negative blood culture plus 1. Participants without a negative blood culture at post-baseline visits were censored at the last assessment date. Kaplan-Meier method was used for analysis. | Day 1 up to maximum of Day 42 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marc Engelhardt | Basilea Pharmaceutica International Ltd, Allschwil | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Netcare Union Hospital Trauma Surgeons | Alberton | Gauteng | 1449 | South Africa | ||
| Milpark Academic Trauma Centre |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37022196 | Result | Vazquez JA, Pappas PG, Boffard K, Paruk F, Bien PA, Tawadrous M, Ople E, Wedel P, Oborska I, Hodges MR. Clinical Efficacy and Safety of a Novel Antifungal, Fosmanogepix, in Patients with Candidemia Caused by Candida auris: Results from a Phase 2 Trial. Antimicrob Agents Chemother. 2023 May 17;67(5):e0141922. doi: 10.1128/aac.01419-22. Epub 2023 Apr 6. |
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| ID | Title | Description |
|---|---|---|
| FG000 | APX001 (Fosmanogepix) | Participants with candidemia and/or invasive candidiasis caused by Candida auris and with limited antifungal treatment options were administered APX001. On Day 1, participants received APX001 1000 milligrams (mg) as a loading dose over 3 hours by intravenous (IV) infusion twice daily (BID). On Days 2 and 3, participants received APX001 600 mg as maintenance dose over 3 hours by IV infusion once daily (QD). On Day 4 and onwards, maintenance dose was administered as either APX001 600 mg IV infusion QD over 3 hours or APX001 800 mg orally QD. Participants who were clinically stable after 3 days of IV administration and could swallow tablets, could switch from IV to oral dosing from Day 4 and onwards. Maximum treatment duration was of 42 days. Participants were followed up for 4 weeks (+ 4 days) post last dose of study drug. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Analysis was performed on all enrolled participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | APX001 (Fosmanogepix) | Participants with candidemia and/or invasive candidiasis caused by Candida auris and with limited antifungal treatment options were administered APX001. On Day 1, participants received APX001 1000 mg as a loading dose over 3 hours by IV infusion BID. On Days 2 and 3, participants received APX001 600 mg as maintenance dose over 3 hours by IV infusion QD. On Day 4 and onwards, maintenance dose was administered as either APX001 600 mg IV infusion QD over 3 hours or APX001 800 mg orally QD. Participants who were clinically stable after 3 days of IV administration and could swallow tablets, could switch from IV to oral dosing from Day 4 and onwards. Maximum treatment duration was of 42 days. Participants were followed up for 4 weeks (+ 4 days) post last dose of study drug. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Treatment Success at End of Study Treatment (EOST) as Determined by Data Review Committee (DRC) | Treatment success was defined as meeting all of the following criteria: 1) Two consecutive blood cultures negative for Candida species, and/or for participants with a deep-seated site of infection, at least 1 negative tissue culture or aspirate/fluid culture. For participants with a deep-seated site of infection involving visceral organs from which a tissue culture was not obtainable, resolution of the attributable clinical signs of infection recorded at Baseline, and as applicable, radiological improvement associated with the site of infection. 2) Alive at EOST and 3) No concomitant use of any other systemic antifungal therapies through EOST. | The modified intent-to-treat (mITT) population included all participants who received at least 1 dose of study drug and had a confirmed diagnosis of candidemia and/or invasive candidiasis caused by Candida auris within 120 hours (for candidemia) or 168 hours (for invasive candidiasis without candidemia) of study qualification (as determined by the DRC). | Posted | Number | 95% Confidence Interval | Percentage of participants | EOST: any day from Day 1 up to maximum of Day 42 |
Day 1 up to maximum of 32 days of follow up post last dose of study drug, where maximum treatment duration was 42 days (maximum up to 74 days)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | APX001 (Fosmanogepix) | Participants with candidemia and/or invasive candidiasis caused by Candida auris and with limited antifungal treatment options were administered APX001. On Day 1, participants received APX001 1000 mg as a loading dose over 3 hours by IV infusion BID. On Days 2 and 3, participants received APX001 600 mg as maintenance dose over 3 hours by IV infusion QD. On Day 4 and onwards, maintenance dose was administered as either APX001 600 mg IV infusion QD over 3 hours or APX001 800 mg orally QD. Participants who were clinically stable after 3 days of IV administration and could swallow tablets, could switch from IV to oral dosing from Day 4 and onwards. Maximum treatment duration was of 42 days. Participants were followed up for 4 weeks (+ 4 days) post last dose of study drug. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac arrest | Cardiac disorders | MedDRA v22.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina pectoris | Cardiac disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Basilea Pharmaceutica International Ltd, Allschwil | +41 79 701 0551 | marc.engelhardt@basilea.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 8, 2020 | Dec 13, 2022 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 8, 2021 | Dec 13, 2022 | SAP_003.pdf |
| ID | Term |
|---|---|
| D058387 | Candidemia |
| D058365 | Candidiasis, Invasive |
| D002177 | Candidiasis |
| ID | Term |
|---|---|
| D009181 | Mycoses |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D000072742 | Invasive Fungal Infections |
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Open-label, single arm intervention. All patients will receive APX001. On Days 1-3, APX001 will be administered intravenously. Thereafter, if the patient is able to take oral medication, APX001 tablets will be taken orally.
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|
| Percentage of Participants With Mycological Outcomes at EOST and 2 and 4 Weeks After EOST | Mycological outcomes were determined based on eradication and presumed eradication. Eradication was defined as a negative blood (and/or other infection site) culture(s) for Candida species. Presumed eradication (applicable to invasive candidiasis) was defined as clinical resolution of invasive Candida species infection where tissue samples were unavailable. These would be applicable only if there were no concomitant or additional systemic antifungal usage. | EOST: any day from Day 1 up to maximum of Day 42, 2 and 4 weeks after EOST |
| Percentage of Participants With Treatment Success at EOST Determined by Investigator | Treatment success was defined as meeting all of the following criteria: 1) Two consecutive blood cultures negative for Candida species, and/or for participants with a deep-seated site of infection, at least 1 negative tissue culture or aspirate/fluid culture. For participants with a deep-seated site of infection involving visceral organs from which a tissue culture was not obtainable, resolution of the attributable clinical signs of infection recorded at Baseline, and as applicable, radiological improvement associated with the site of infection. 2) Alive at EOST and 3) No concomitant use of any other systemic antifungal therapies through EOST. | EOST: any day from Day 1 up to maximum of Day 42 |
| Percentage of Participants With Treatment Success at 2 and 4 Weeks After EOST Determined by Investigator and by the DRC | Treatment success was defined as meeting all of the following criteria: 1) Two consecutive blood cultures negative for Candida species, and/or for participants with a deep-seated site of infection, at least 1 negative tissue culture or aspirate/fluid culture. For participants with a deep-seated site of infection involving visceral organs from which a tissue culture was not obtainable, resolution of the attributable clinical signs of infection recorded at Baseline, and as applicable, radiological improvement associated with the site of infection. 2) Alive at EOST and 3) No concomitant use of any other systemic antifungal therapies through EOST. | 2 and 4 weeks after EOST (where EOST is any day from Day 1 up to maximum of Day 42) |
| All-Cause Mortality Through Study Day 30 | Percentage of participants who died through study Day 30 is reported in this outcome measure. | Day 1 through Day 30 |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between first dose of study drug and up to Week 4 (+4 days) post last dose of study drug that were absent before treatment or that worsened relative to pretreatment state. | Day 1 up to maximum of 32 days of follow up post last dose of study drug, where maximum treatment duration was 42 days (maximum up to 74 days) |
| Johannesburg |
| Gauteng |
| 2193 |
| South Africa |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | APX001 (Fosmanogepix) | Participants with candidemia and/or invasive candidiasis caused by Candida auris and with limited antifungal treatment options were administered APX001. On Day 1, participants received APX001 1000 mg as a loading dose over 3 hours by IV infusion BID. On Days 2 and 3, participants received APX001 600 mg as maintenance dose over 3 hours by IV infusion QD. On Day 4 and onwards, maintenance dose was administered as either APX001 600 mg IV infusion QD over 3 hours or APX001 800 mg orally QD. Participants who were clinically stable after 3 days of IV administration and could swallow tablets, could switch from IV to oral dosing from Day 4 and onwards. Maximum treatment duration was of 42 days. Participants were followed up for 4 weeks (+ 4 days) post last dose of study drug. |
|
|
| Secondary | Time to First Negative Blood Culture | Time to first negative blood culture was defined as the number of days from date of first dose of study drug to the date of first negative blood culture plus 1. Participants without a negative blood culture at post-baseline visits were censored at the last assessment date. Kaplan-Meier method was used for analysis. | The mITT population included all participants who received at least 1 dose of study drug and had a confirmed diagnosis of candidemia and/or invasive candidiasis caused by Candida auris within 120 hours (for candidemia) or 168 hours (for invasive candidiasis without candidemia) of study qualification (as determined by the DRC). Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Days | Day 1 up to maximum of Day 42 |
|
|
|
| Secondary | Percentage of Participants With Mycological Outcomes at EOST and 2 and 4 Weeks After EOST | Mycological outcomes were determined based on eradication and presumed eradication. Eradication was defined as a negative blood (and/or other infection site) culture(s) for Candida species. Presumed eradication (applicable to invasive candidiasis) was defined as clinical resolution of invasive Candida species infection where tissue samples were unavailable. These would be applicable only if there were no concomitant or additional systemic antifungal usage. | The mITT population included all participants who received at least 1 dose of study drug and had a confirmed diagnosis of candidemia and/or invasive candidiasis caused by Candida auris within 120 hours (for candidemia) or 168 hours (for invasive candidiasis without candidemia) of study qualification (as determined by the DRC). | Posted | Number | 95% Confidence Interval | Percentage of participants | EOST: any day from Day 1 up to maximum of Day 42, 2 and 4 weeks after EOST |
|
|
|
| Secondary | Percentage of Participants With Treatment Success at EOST Determined by Investigator | Treatment success was defined as meeting all of the following criteria: 1) Two consecutive blood cultures negative for Candida species, and/or for participants with a deep-seated site of infection, at least 1 negative tissue culture or aspirate/fluid culture. For participants with a deep-seated site of infection involving visceral organs from which a tissue culture was not obtainable, resolution of the attributable clinical signs of infection recorded at Baseline, and as applicable, radiological improvement associated with the site of infection. 2) Alive at EOST and 3) No concomitant use of any other systemic antifungal therapies through EOST. | The mITT population included all participants who received at least 1 dose of study drug and had a confirmed diagnosis of candidemia and/or invasive candidiasis caused by Candida auris within 120 hours (for candidemia) or 168 hours (for invasive candidiasis without candidemia) of study qualification (as determined by the DRC). | Posted | Number | 95% Confidence Interval | Percentage of participants | EOST: any day from Day 1 up to maximum of Day 42 |
|
|
|
| Secondary | Percentage of Participants With Treatment Success at 2 and 4 Weeks After EOST Determined by Investigator and by the DRC | Treatment success was defined as meeting all of the following criteria: 1) Two consecutive blood cultures negative for Candida species, and/or for participants with a deep-seated site of infection, at least 1 negative tissue culture or aspirate/fluid culture. For participants with a deep-seated site of infection involving visceral organs from which a tissue culture was not obtainable, resolution of the attributable clinical signs of infection recorded at Baseline, and as applicable, radiological improvement associated with the site of infection. 2) Alive at EOST and 3) No concomitant use of any other systemic antifungal therapies through EOST. | The mITT population included all participants who received at least 1 dose of study drug and had a confirmed diagnosis of candidemia and/or invasive candidiasis caused by Candida auris within 120 hours (for candidemia) or 168 hours (for invasive candidiasis without candidemia) of study qualification (as determined by the DRC). Here, "Overall Number of Participants Analyzed"=participants evaluable for this outcome measure and "number analyzed"= number of participants evaluable for specified rows. | Posted | Number | 95% Confidence Interval | Percentage of participants | 2 and 4 weeks after EOST (where EOST is any day from Day 1 up to maximum of Day 42) |
|
|
|
| Secondary | All-Cause Mortality Through Study Day 30 | Percentage of participants who died through study Day 30 is reported in this outcome measure. | The mITT population included all participants who received at least 1 dose of study drug and had a confirmed diagnosis of candidemia and/or invasive candidiasis caused by Candida auris within 120 hours (for candidemia) or 168 hours (for invasive candidiasis without candidemia) of study qualification (as determined by the DRC). | Posted | Number | Percentage of participants | Day 1 through Day 30 |
|
|
|
| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between first dose of study drug and up to Week 4 (+4 days) post last dose of study drug that were absent before treatment or that worsened relative to pretreatment state. | Safety population included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Day 1 up to maximum of 32 days of follow up post last dose of study drug, where maximum treatment duration was 42 days (maximum up to 74 days) |
|
|
|
| 2 |
| 9 |
| 2 |
| 9 |
| 9 |
| 9 |
| Multiple organ dysfunction syndrome | General disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA v22.0 | Non-systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Generalised oedema | General disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Hypothermia | General disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA v22.0 | Non-systematic Assessment |
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| Pneumonia bacterial | Infections and infestations | MedDRA v22.0 | Non-systematic Assessment |
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| Bacteraemia | Infections and infestations | MedDRA v22.0 | Non-systematic Assessment |
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| Bacterial sepsis | Infections and infestations | MedDRA v22.0 | Non-systematic Assessment |
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| Conjunctivitis | Infections and infestations | MedDRA v22.0 | Non-systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA v22.0 | Non-systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Muscle atrophy | Musculoskeletal and connective tissue disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Seizure | Nervous system disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Adjustment disorder with depressed mood | Psychiatric disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Confusional state | Psychiatric disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA v22.0 | Non-systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA v22.0 | Non-systematic Assessment |
|
The Sponsor has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| D016469 |
| Fungemia |
| D018805 | Sepsis |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Title | Measurements |
|---|---|
|
|
| 2 Weeks after EOST: Investigator |
|
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| 4 Weeks after EOST: Investigator |
|
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