Neptuno: Trial to Determine the Efficacy/Safety of Plitidepsin vs Control in Patients With Moderate COVID-19 Infection
Study Details
Study Description
Brief Summary
Treatment of patients hospitalised for management of moderate COVID-19 infection
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
This is a multicentre, open-label, controlled Phase 3 study in which adults requiring hospital admission and O2 supplementation for management of moderate COVID-19 infection will be randomised in 1:1:1 to: Plitidepsin 1.5 mg arm, Plitidepsin 2.5 mg arm and Control arm
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Plitidepsin 1.5 mg arm Patients will receive plitidepsin 1.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3. |
Drug: Plitidepsin
Plitidepsin 2 mg powder is provided as a sterile, preservative-free, and white to off-white lyophilised powder/cake comprising 2 mg plitidepsin and mannitol in a single-dose, 10 mL clear type 1 glass vial.
Solvent for plitidepsin is provided as a sterile, preservative-free, clear, slightly viscous aqueous liquid (4 mL) containing macrogolglycerol ricinoleate and ethanol in a single-dose type 1 clear glass ampoule.
For administration, vial contents are reconstituted by addition of 4 mL of solvent for plitidepsin to obtain a slightly yellowish solution containing 0.5 mg/mL plitidepsin with mannitol, macrogolglycerol ricinoleate and ethanol excipients. The required amount of plitidepsin reconstituted solution is added to bag containing 0.9% sodium chloride or 5% glucose for IV injection and administered as an IV infusion over 60 minutes.
Drug: Dexamethasone
Detailed information about the formulation, posology, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions.
|
| Experimental: Plitidepsin 2.5 mg arm Patients will receive plitidepsin 2.5 mg/day IV in addition to dexamethasone on days 1 to 3. |
Drug: Plitidepsin
Plitidepsin 2 mg powder is provided as a sterile, preservative-free, and white to off-white lyophilised powder/cake comprising 2 mg plitidepsin and mannitol in a single-dose, 10 mL clear type 1 glass vial.
Solvent for plitidepsin is provided as a sterile, preservative-free, clear, slightly viscous aqueous liquid (4 mL) containing macrogolglycerol ricinoleate and ethanol in a single-dose type 1 clear glass ampoule.
For administration, vial contents are reconstituted by addition of 4 mL of solvent for plitidepsin to obtain a slightly yellowish solution containing 0.5 mg/mL plitidepsin with mannitol, macrogolglycerol ricinoleate and ethanol excipients. The required amount of plitidepsin reconstituted solution is added to bag containing 0.9% sodium chloride or 5% glucose for IV injection and administered as an IV infusion over 60 minutes.
Drug: Dexamethasone
Detailed information about the formulation, posology, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions.
|
| Active Comparator: Control arm Patients will receive dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, patients in this group may receive a regulatory-approved antiviral treatment. |
Drug: Dexamethasone
Detailed information about the formulation, posology, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions.
Drug: Remdesivir
Detailed information about the formulation, posology, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions.
Drug: Favipiravir
Detailed information about the formulation, posology, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions.
|
Outcome Measures
Primary Outcome Measures
- To compare efficacy of plitidepsin 1.5 mg or 2.5 mg versus the control assessing the need of supplementary oxygen: Time to sustained withdrawal of supplementary oxygen with no subsequent reutilisation during remaining study period [From administration date to Day 31(±3)]
Time to sustained withdrawal of supplementary oxygen (as defined by the WHO clinical progression scale (Score ≤4). The WHO clinical progression scale provides a measure of illness severity across a range from 0 (uninfected) to 10 (dead).
Secondary Outcome Measures
- Time to sustained (i.e., with no subsequent readmission to Day 31) hospital discharge (since randomisation). [From administration date to Day 31(±3)]
- Clinical status by the 11-category WHO Clinical Progression Scale [Day 8 (±1)]
The WHO clinical progression scale provides a measure of illness severity across a range from 0 (uninfected) to 10 (dead).
- Total duration of advanced oxygen support (high-flow nasal oxygen, extracorporeal membrane oxygenation -ECMO-, non-invasive ventilation or mechanical ventilation). [From administration date to Day 31(±3)]
- Percentage of patients in each study group requiring admission to ICU [Day 4, Day 8(±1) , Day 15(±1) and Day 31(±3)]
- Frequency of adverse events [From administration date to Day 31(±3)]
Adverse Event Types according to the National Cancer Institute [NCI]-Common Terminology Criteria for AEs (CTCAE v.5.0): treatment-emergent adverse events (TEAEs), TEAEs ≥ grade 3, adverse events of special interest (AESIs), serious adverse events (SAEs), drug-related serious adverse events (i.e., SARs) and adverse events leading to treatment discontinuation
- Frequency of deaths [From administration date to Day 31(±3)]
- Change from baseline in haematology laboratory parameters [Screening (Day 0-1), Days 1, 2, 3, 4, Day 8(±1), and Day 31(±3)]
Haematology laboratory parameters: red blood cell (RBC) [cells10^6/µL], haemoglobin [g/dL], haematocrit [%], white blood cell (WBC) with differential [cells10^3/µL], and platelet count [cells10^3/µL]
- Change from baseline in coagulation laboratory parameter: D-dimer [mg/L] [Day 1, 2, 3, 4, Day 8(±1) and Day 31(±3)]
- Change from baseline in serum chemistry parameters [Screening (Day 0-1), Days 1, 2, 3, 4, Day 8(±1) and Day 31(±3)]
Serum chemistry parameters: alanine transaminase (ALT) [U/L], aspartate transaminase (AST) [U/L], alkaline phosphatase [U/L], gamma glutamyl transferase (GGT) [U/L], lactate dehydrogenase (LDH) [U/L], total bilirubin [mg/dL], direct bilirubin [mg/dL], glucose (fasting) (mg/dL), sodium [mEq/L], potassium [mEq/L], calcium (albumin adjusted calculation) [mEq/L], magnesium [mEq/L], blood urea nitrogen (BUN) [mg/dL], creatinine [mg/dL], calculated creatinine clearance (Cockcroft-Gault equation) [ml/min], creatine-phosphokinase (CPK) [U/L], albumin [g/dL], amylase [U/L], lipase [U/L], procalcitonin [ng/mL], and Troponin [ng/L] (I or T according to local practice for screening)
- Change from baseline in serum chemistry parameter: Troponin T [ng/L] (high sensitivity) [Day 1, Day 8(±1) and Day 31(±3)]
- Change from baseline in serum chemistry parameter: N-terminal pro b-type natriuretic peptide (NT-pro BNP: pmol/L) [Day 1, Day 8(±1) and Day 31(±3)]
- Safety/Tolerability: Change from baseline in serological SARS CoV 2 testing (immunoglobulin [Ig]G) [UA/ml] [Day 1 and Day 31(±3)]
- Safety/Tolerability: Change from baseline in inflammatory biomarkers [Days 1, 2, 3, 4, Day 8(±1) and Day 31(±3)]
Proinflammatory biomarkers: C-reactive protein (CRP) [mg/L], ferritin [ng/L], IL-1β [pg/mL], IL-6 [pg/mL], IL-10 [pg/mL] and tumour necrosis factor alpha (TNFα) [pg/mL]
- Change from baseline in vital signs [Screening (Day 0-1), Once daily while the patient is hospitalized, and on Day 8(±1) and Day 31(±3)]
Vital signs: temperature [°C or °F], sitting blood pressure [mmHg], heart rate [beats per minute], respiratory rate [breaths per minute], saturation of oxygen (SpO2) at room air [%]by pulse oximetry or arterial blood gas analyses and its respective FiO2 [%],
- Change from baseline in electrocardiogram (ECG) findings [Screening and on Days 1, 3, and Day 31(±3)]
ECG findings: QTcF prolongation and any QTcF values >500 msec
Other Outcome Measures
- Percentage of patients in each study group who require hospital readmission related to COVID-19 [From administration date to Day 31(±3)]
- Percentage of patients in each study group and in each of the categories of the 11-point WHO Clinical Progression Scale [Day 4, Day 8(±1), Day 15(±1) and Day 31(±3)]
Percentage of patients in each study group requiring oxygen therapy, requiring non-invasive mechanical ventilation and requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). The WHO clinical progression scale provides a measure of illness severity across a range from 0 (uninfected) to 10 (dead).
- Time to intensification of respiratory support (WHO >6 [intubation]) [From administration date to Day 31(±3)]
The WHO clinical progression scale provides a measure of illness severity across a range from 0 (uninfected) to 10 (dead).
- Total duration of intensive care unit (ICU) stay for each study group. [From administration date to Day 31(±3)]
- Time to initiation with immune-modulating drugs [From administration date to Day 31(±3)]
- Time to initiation with antiviral drugs [From administration date to Day 31(±3)]
- Percentage of patients receiving subsequent immune-modulating drugs [Day 4, Day 8(±1), Day 15(±1), and Day 31(±3)]
- Percentage of patients receiving subsequent antiviral drugs [Day 4, Day 8(±1), Day 15(±1), and Day 31(±3)]
- Percentage of patients in each study group with nosocomial infection [Day 4, Day 8(±1), Day 15(±1), and Day 31(±3)]
- Mortality in each study group [Day 4, Day 8(±1), Day 15(±1), and Day 31(±3)]
- Change in the viral load of acute respiratory distress syndrome due to coronavirus 2 (SARS-CoV-2) [copies/mL] in each study group [Day 1 before administration of the study drug until Day 8(±1)]
- Percentage of patients in each study group with undetectable viral load of SARS-CoV-2 [Day 8(±1)]
- Efficacy: Change from baseline in inflammatory biomarkers [From baseline until Days 2, 3, 4, Day 8(±1), and Day 31(±3)]
Proinflammatory biomarkers: C-reactive protein (CRP) [mg/L], ferritin [ng/L], IL-1β [pg/mL], IL-6 [pg/mL], IL-10 [pg/mL] and tumour necrosis factor alpha (TNFα) [pg/mL]
- Efficacy: Change from baseline in serological SARS CoV 2 testing (immunoglobulin [Ig]G) [UA/ml] [Day 1 and Day 31(±3)]
- To compare efficacy in the primary endpoint and describe safety/tolerability of pooled plitidepsin arms versus control: Time to sustained withdrawal of supplementary oxygen with no subsequent reutilisation during remaining study period [From administration date to Day 31(±3)]
Time to sustained withdrawal of supplementary oxygen (as defined by the WHO clinical progression scale (Score ≤4)). The WHO clinical progression scale provides a measure of illness severity across a range from 0 (uninfected) to 10 (dead).
- To compare efficacy in the primary endpoint and describe safety/tolerability between plitidepsin arms (1.5 versus 2.5 mg): Time to sustained withdrawal of supplementary oxygen with no subsequent reutilisation during remaining study period [From administration date to Day 31(±3)]
To compare efficacy in the primary endpoint and describe safety/tolerability between plitidepsin arms (1.5 versus 2.5 mg) in case both are significantly superior to the control. Time to sustained withdrawal of supplementary oxygen (as defined by the WHO clinical progression scale (Score ≤4). The WHO clinical progression scale provides a measure of illness severity across a range from 0 (uninfected) to 10 (dead).
- To explore the influence of risk factors or scores for clinical deterioration that were not individually included; Obesity, hypertension, age and individual co-morbidities included in the Charlson Index, ISARIC-4C score or vaccination status. [From administration date to Day 31(±3)]
- Time to sustained sustained withdrawal of supplementary oxygen with no subsequent reutilisation during remaining study period, before (protocol v.6) and after the amendment (protocol v.7). [From administration date to Day 31(±3)]
Time to sustained withdrawal of supplementary oxygen (as defined by the WHO clinical progression scale (Score ≤4). The WHO clinical progression scale provides a measure of illness severity across a range from 0 (uninfected) to 10 (dead).
- Time to sustained (i.e., with no subsequent readmission to Day 31) hospital discharge (since randomisation), before (protocol v.6) and after the amendment (protocol v.7). [From administration date to Day 31(±3)]
- Substudy only: Change from baseline in electrocardiogram (ECG) findings [0, 1, 2.5, 5, 24, 25, 26.5, 29, 48, and 49 hours]
Electrocardiogram (ECG) findings: heart rate, QTc, QRS, waveform morphology-related measurements and QTc for whole blood concentrations of plitidepsin (ng/ml)
- Substudy only: Whole blood clearance of plitidepsin [0, 1, 2.5, 5, 24, 25, 26.5, 29, 48, 49 and 72 hours]
- Substudy only: Whole blood area under curve (AUC) of plitidepsin [0, 1, 2.5, 5, 24, 25, 26.5, 29, 48, 49 and 72 hours]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Signed informed consent obtained prior to initiation of any study-specific procedures and study treatment.
-
Documented diagnosis of SARS-CoV-2 infection, determined by either qualitative polymerase chain reaction (PCR), antigen test by local laboratory, or any other validated method approved by the local health authority, from appropriate biological samples collected no more than 72 hours prior to study treatment on Day 1.
-
Patient meets category 5 on the 11-point WHO Clinical Progression Scale: requires hospitalisation and oxygen by mask or nasal prongs/cannula.
-
A maximum of 14 days from onset of COVID-19 symptoms to initiation of study treatment on Day 1.
-
Male or female aged ≥18 years.
-
Adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory:
-
Absolute neutrophil count ≥500/mm3 (0.5 x 109/L).
-
Platelet count ≥75,000/mm3 (75 x 109/L).
-
Alanine transaminase (ALT), aspartate transaminase (AST) ≤3 x upper limit of normal (ULN).
-
Serum bilirubin ≤1 x ULN (or direct bilirubin <1 x ULN when total bilirubin is above ULN).
-
Calculated creatinine clearance ≥30 mL/min (Cockcroft-Gault equation).
-
Creatine phosphokinase (CPK) ≤2.5 x ULN except if the patient has had recent (i.e., in the last week) shivering episodes or trauma. In that case, the level of CPK should be ≤5 x ULN.
-
Agree not to participate in another interventional clinical trial through Day 31.
-
Females of reproductive capacity must have a negative serum or urine pregnancy test by local laboratory at study enrolment and must be non-lactating.
-
Females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin. Patients in the control arm must use effective contraception during the time indicated in the approved product information (summary of product characteristics [SmPC] or leaflet). If no information is available in the approved product information, patients in the control arm must use effective contraception for at least one week after the study completion or the time indicated based on the investigator's discretion.
Exclusion Criteria:
-
Subjects with a pre-baseline (i.e., in the month preceding the current COVID-19 infection) impairment in general health condition for whatever reason except COVID-19, with a severe dependency for daily living activities (Barthel index ≤ 60/100) or chronic oxygen therapy.
-
Having received treatment for COVID-19 in another clinical trial in the prior 4 weeks, except documented allocation in a placebo arm.
-
Evidence of respiratory failure at the time of randomisation, based on resource utilisation requiring at least one of the following: endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, non-invasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure (i.e., clinical need for one of the aforementioned therapies, which could not be administered in a resource-limited setting).
-
Patients with severe COVID-19, meeting score >5 on the 11-point WHO Clinical Progression Scale or presenting, after an initial stabilisation prior to randomisation, any of clinical signs indicative of severe systemic illness, such as respiratory rate ≥30 per minute, heart rate ≥125 per minute, or PaO2/FiO2 <300. In case a direct measure of PaO2 has not been obtained, it should be imputed according to a referenced formula. For sites located over 1000 m above sea level, PaO2/FiO2 ratio will be adjusted.
-
Patients receiving, at randomisation, treatment with antiviral therapy against SARS-CoV-2 or requiring anti-inflammatory/immunomodulating drugs beyond glucocorticoids with the exceptions listed below:
- Prior administration of dexamethasone or equivalent glucocorticoid might be acceptable if:
-
The total daily dose is not higher than 10 mg of dexamethasone phosphate (equivalent to dexamethasone base 8.25 mg/day) or equivalent glucocorticoids.
-
The duration of the treatment does not exceed 72 hours prior to study treatment Day 1.
- Prior administration of dexamethasone or equivalent glucocorticoid might be acceptable if:
-
The total daily dose is not higher than 10 mg of dexamethasone phosphate (equivalent to dexamethasone base 8.25 mg/day) or equivalent glucocorticoids.
-
The duration of the treatment does not exceed 72 hours prior to study treatment Day 1.
- Prior administration of an antiviral might be acceptable in the following circumstances:
-
For small molecules (e.g., remdesivir, molnupiravir, nirmaltrevir/ritonavir), they must have been given for an earlier stage of the disease, outside a clinical trial, and there should be a documentation of objective clinical deterioration plus evidence of persisting positivity for SARS-CoV-2 in appropriate biological samples. Last dose of previous antiviral drugs should have been administered at least 24 h before randomisation.
-
For antiviral monoclonal antibodies, they must have been given for an earlier stage of the disease (including pre-exposure prophylaxis), outside a clinical trial, and there should be a documentation of objective clinical deterioration plus evidence of persisting positivity for SARS-CoV-2 in appropriate biological samples. Last dose of antiviral monoclonal antibodies should have been administered at least 1 week before randomisation.
-
Patients receiving treatment with chloroquine or derivatives within 8 weeks before enrolment or during the study.
-
Patients receiving treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers.
-
Viral illness (other than COVID-19) requiring therapy, except for patients with treated and adequately controlled (undetectable) human immunodeficiency virus infection.
-
Patients with uncontrolled known primary or secondary immunodeficiency, including chronic treatment with glucocorticoids (i.e., prednisone at a daily dose of >10 mg for
1 month, or another glucocorticoid at equipotent dose).
- Any of the following cardiac conditions or risk factors:
-
Sinus bradycardia (<50 beats/min), sinus nodal dysfunction (sick sinus disease), atrioventricular block of any degree (PR >200 msec), or any other bradyarrhythmia (<50 beats/min), except for patients with permanent pacemakers;
-
Cardiac infarction, cardiac surgery or cardiac insufficiency episode within the last 6 months;
-
Known abnormal value of left ventricular ejection fraction (LVEF <low limit of normal (LLN)), unless documented confirmation of recovery (LVEF >LLN) in the previous month;
-
QT interval corrected using Fridericia's formula (QTcF) >450 msec for males or
470 msec for females;
-
History of known congenital or acquired QT prolongation;
-
Uncorrected hypokalaemia, hypocalcaemia (adjusted) and/or hypomagnesemia at screening;
-
Troponin test performed at local laboratory >1.5 x ULN; or
-
Need for an unreplaceable drug that prolongs QT and it is clearly associated with a known risk for torsades de pointes (TdP); in case of being already on treatment with these aforementioned drugs, a minimum of 4 half-lives of the drug is required before replacement (if feasible).
-
Hypersensitivity to the active ingredient or any of the excipients (mannitol, macrogolglycerol hydroxystearate, and ethanol) or patients for whom dexamethasone, antihistamine H1/H2 or antiserotoninergic agents are contraindicated.
-
Females who are pregnant (negative serum or urine pregnancy test required for all females of child-bearing potential at screening) or breast feeding.
-
Females and males with partners of child-bearing potential (females who are not surgically sterile or postmenopausal defined as amenorrhea for >12 months) who are not using at least 1 protocol specified method of contraception.
-
Any other clinically significant medical condition (including major surgery within the last 3 weeks before screening) or laboratory abnormality that, in the opinion of the investigator, would jeopardise the safety of the patient or potentially impact on patient compliance or the safety/efficacy observations in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Instituto Medico Platense S.A. | La Plata | Buenos Aires | Argentina | 1900 |
| 2 | Clinica Privada Monte Grande S.A | Monte Grande | Buenos Aires | Argentina | 1842 |
| 3 | Clinica Central S.A. | Villa Regina | Rio Negro | Argentina | 8336 |
| 4 | Sanatorio Parque - Rosario | Rosario | Santa Fe | Argentina | 2000 |
| 5 | Hospital General Agudos Ignacio | Buenos Aires | Argentina | 1428 CABA | |
| 6 | Hospital Francisco Muñiz | Ciudad autónoma de Buenos Aires | Argentina | C1282AEN CABA | |
| 7 | Hospital Rawson | Cordoba | Argentina | 5000 | |
| 8 | Hospital São Rafael | Salvador | BA | Brazil | 41253-190 |
| 9 | Hospital Felicio Rocho | Belo Horizonte | MG | Brazil | 30110-934 |
| 10 | Santa Casa de Misericordia de Passos | Passos | MG | Brazil | 37902-413 |
| 11 | CePCLIN - Centro de Estudos e Pesquisas em Moléstias Infecciosas Ltda | Natal | RN | Brazil | 59025-050 |
| 12 | Hospital Moinhos de Vento (HMV) | Porto Alegre | RS | Brazil | 90035-001 |
| 13 | Hospital São José | Criciúma | SC | Brazil | 88801-250 |
| 14 | CEMEC - Centro Multidisciplinar de Estudos Clínicos | São Bernardo Do Campo | Brazil | 09715-090 | |
| 15 | University Multiprofile Hospital for Active Treatment Sveta Ekaterina EAD | Dimitrovgrad | Bulgaria | 6400 | |
| 16 | Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases - Haskovo | Haskovo | Bulgaria | 6300 | |
| 17 | MHAT "Dr. Nikola Vasiliev" AD | Kyustendil | Bulgaria | 2500 | |
| 18 | Military Medical Academy - MBAL Pleven | Pleven | Bulgaria | 5800 | |
| 19 | "Specialised Hospital for Active Treatment for Pneumophthisiatric Diseases Dr. Dimitar Gramatikov - Ruse" Ltd Department of Pneumology and Phthisiatry | Ruse | Bulgaria | 7000 | |
| 20 | SHATPPD Dr. Dimitar Gramatikov, Ruse Ltd. | Ruse | Bulgaria | 7002 | |
| 21 | University First MHAT "St.Yoan Krastitel"-Sofia EAD | Sofia | Bulgaria | 1142 | |
| 22 | University Multiprofile Hospital for Active Treatment ACIBADEM CITY CLINIC TOKUDA HOSPIAL | Sofia | Bulgaria | 1407 | |
| 23 | "MHAT "Sveta Anna"" - Sofia AD | Sofia | Bulgaria | 1570 | |
| 24 | CliniSalud del Sur S.A.S - Centro de Investigación | Envigado | Antioquia | Colombia | 55422 |
| 25 | Organización Clinica Bonnadona Prevenir S.A.S | Barranquilla | Atlantico | Colombia | 080020 |
| 26 | Clínica de la Costa Ltda. | Barranquilla | Atlántico | Colombia | 80020 |
| 27 | Hospital Universitario MEDERI | Bogotá | Bogotá D.C. | Colombia | 111911 |
| 28 | Caja de Compensacion Familiar de Caldas | Manizales | Caldas | Colombia | 170003 |
| 29 | CH Valence | Valence | Drome | France | 26953 |
| 30 | Centre Hospitalier Universitaire (CHU) Dijon Bourgogne - Hopital Francois Mitterand | Dijon | France | 21079 | |
| 31 | Nouvel Hôpital Civil Service des maladies infectieuses | Strasbourg | France | 67091 | |
| 32 | Centre Hospitalier Regional et Universitaire de Tours (CHRU Tours) - Hopital Bretonneau | Tours | France | 37044 | |
| 33 | Democritus University Hospital University General Hospital of Alexandroupolis | Alexandroupoli | Greece | 68100 | |
| 34 | Evangelismos Hospital General Hospital of Athens Evangelismos, Intensive Care Unit | Athens | Greece | 106 76 | |
| 35 | Sotiria Hospital General Hospital of Chest Diseases of Athens "Sotiria" 3rd Department of Internal Medicine of University of Athens | Athens | Greece | 115 27 | |
| 36 | General Hospital of Athens Alexandra | Athens | Greece | 115 28 | |
| 37 | General Hospital of Athens "Laiko", University of Athens Agiou | Athens | Greece | 11527 | |
| 38 | Attikon Hospital | Chaïdári | Greece | 12462 | |
| 39 | Tzaneio Hospital General Hospital of Piraeus Tzaneio | Piraeus | Greece | 185 36 | |
| 40 | Hospital Cardiologica Aguascalientes | Aguascalientes | Ags | Mexico | 20230 |
| 41 | Hospital Médica Sur | Mexico City | Cdmx | Mexico | 14050 |
| 42 | INER | Mexico City | Cdmx | Mexico | 14080 |
| 43 | Sanatorio Palmore, A.C. | Chihuahua | CHH | Mexico | 31020 |
| 44 | Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán | Mexico City | DIF | Mexico | 14000 |
| 45 | Centro de Investigación Clínica Chapultepec | Morelia | Michoacan | Mexico | 58260 |
| 46 | Universidad Autonoma de Nuevo Leon - Hospital Universitario "Dr. Jose Eleuterio Gonzalez" | Monterrey | NL | Mexico | 64460 |
| 47 | Hospital Alberto Sabogal Sologuren | Bellavista | Lima | Peru | Callao 2 |
| 48 | Hospital de Chancay | Chancay | Lima | Peru | 15131 |
| 49 | Hospital Nacional Hipolito Unanue (HNHU) | El Agustino | Lima | Peru | 15007 |
| 50 | Universidad Peruana Cayetano Heredia (UPCH) - Hospital Cayetano Heredia (HCH) | Lima Cercado | Lima | Peru | 10680 |
| 51 | HULC - Hospital de Curry Cabral | Lisboa | Portugal | 1069-166 | |
| 52 | Spitalul Clinic De Boli Infectioase Cluj-Napoca, Sectia HIV/SIDA | Cluj-Napoca | Cluj | Romania | 400000 |
| 53 | "Hospital of Infectious Diseases and Pneumology ""Victor Babes'' Timisoara " | Timişoara | Timis | Romania | 300310 |
| 54 | Spitalul Clinic de Boli Infectioase Constanta | Constanţa | Tomis | Romania | 900709 |
| 55 | Institutul National De Boli Infectioase "Prof. Dr. Matei Bals" | Bucharest | Romania | 021105 | |
| 56 | Spitalul Clinic de Boli Infectioase si Tropicale Dr. Victor Babes - Bucharest | Bucharest | Romania | 030303 | |
| 57 | Institutul National De Boli Infectioase "Prof. Dr. Matei Bals" | Bucharest | Romania | 21105 | |
| 58 | Spitalul Clinic Universitar de Urgenta Bucuresti | Bucharest | Romania | 50098 | |
| 59 | Spitalul Clinic De Boli Infectioase "Sfanta Parascheva" IASI, Sectia Boli Infectioase III | Iaşi | Romania | 700116 | |
| 60 | Spitalul Judetean de Urgenta 'Sf. Ioan cel Nou' Suceava, Sectia de Boli Infectioase | Suceava | Romania | 720237 | |
| 61 | Netcare Lakeview Hospital | Benoni | Gauteng | South Africa | 1500 |
| 62 | Tiervlei Trial Centre | Cape Town | Western Cape | South Africa | 7530 |
| 63 | TASK eden | George | Western Cape | South Africa | 6530 |
| 64 | Hospital Universitari Germans Trias i Pujol | Badalona | Barcelona | Spain | 08916 |
| 65 | Hospital Universitari de Bellvitge | Hospitalet de Llobregat | Barcelona | Spain | 08907 |
| 66 | Hospital Universitario Puerto Real | Puerto Real | Cádiz.Spain | Spain | 11510 |
| 67 | Hospital Universitario de Jerez de la Frontera | Jerez De La Frontera | Cádiz | Spain | 11407 |
| 68 | Hospital Universitario HM Montepríncipe | Boadilla Del Monte | Madrid | Spain | 28668 |
| 69 | Hospital Universitario de Fuenlabrada | Fuenlabrada | Madrid | Spain | 28942 |
| 70 | Hospital Universitario de Getafe | Getafe | Madrid | Spain | 28905 |
| 71 | HM Puerta del Sur | Móstoles | Madrid | Spain | 28038 |
| 72 | Hospital Universitario de Móstoles | Móstoles | Madrid | Spain | 28935 |
| 73 | Hospital Quirónsalud Madrid | Pozuelo De Alarcón | Madrid | Spain | 28223 |
| 74 | HM Torrelodones | Torrelodones | Madrid | Spain | 28250 |
| 75 | Hospital Costa Del Sol | Marbella | Málaga | Spain | 29603 |
| 76 | Hospital Quirón Marbella | Marbella | Málaga | Spain | 29603 |
| 77 | Hospital Álvaro Cunqueiro | Vigo | Pontevedra | Spain | 36213 |
| 78 | Hospital Universitario de Cruces | Barakaldo | Vizcaya | Spain | 48903 |
| 79 | Hospital General Universitario de Alicante | Alicante | Spain | 3010 | |
| 80 | Complejo Asistencial Universitario de Burgos - Hospital Universitario de Burgos | Burgos | Spain | 9006 | |
| 81 | Universidad de Cadiz (UCA) - Hospital Universitario Puerta del Mar (HUPM) | Cadiz | Spain | 11009 | |
| 82 | Hospital Universitario Virgen de las Nieves (HUVN) | Granada | Spain | 18014 | |
| 83 | Hospital Clinico San Cecilio | Granada | Spain | 18016 | |
| 84 | Hospital Universitario de Guadalajara | Guadalajara | Spain | 19002 | |
| 85 | Hospital Universitari Arnau de Vilanova de Lleida | Lleida | Spain | 25198 | |
| 86 | H.U. La Princesa | Madrid | Spain | 28006 | |
| 87 | Hospital Gregorio Marañón | Madrid | Spain | 28007 | |
| 88 | Hospital Universitario Moncloa | Madrid | Spain | 28008 | |
| 89 | Hospital Infanta Leonor | Madrid | Spain | 28032 | |
| 90 | Hospital Universitario Ramón y Cajal | Madrid | Spain | 28034 | |
| 91 | Fundacion Jimenez Diaz | Madrid | Spain | 28040 | |
| 92 | Hospital Clínico San Carlos | Madrid | Spain | 28040 | |
| 93 | Hospital 12 Octubre | Madrid | Spain | 28041 | |
| 94 | H. HM Sanchinarro | Madrid | Spain | 28050 | |
| 95 | Hospital de Emergencias Enfermera Isabel Zendal | Madrid | Spain | 28055 | |
| 96 | Complexo Hospitalario de Pontevedra | Pontevedra | Spain | 36071 | |
| 97 | Hospital Universitario de Salamanca | Salamanca | Spain | 37007 | |
| 98 | Instituto de Investigación Sanitaria Valdecilla (IDIVAL) | Santander | Spain | 39008 | |
| 99 | Hospital Universitario Virgen del Rocío | Sevilla | Spain | 41013 | |
| 100 | Ege University Medical School, Department of Infectious Diseases and Clinical Microbiology | Bornova | İzmir | Turkey | 35040 |
| 101 | T.C. Saglik Bakanligi Tepecik Egitim ve Arastirma Hastanesi - Enfeksiyon Hastaliklari ve Klinik Mikrobiyoloji Klinigi | Konak | Izmir | Turkey | 35040 |
| 102 | Kocaeli Universitesi - Kocaeli Universitesi Tip Fakultesi - Kocaeli Universitesi Arastirma ve Uygulama Hastanesi | İzmit | Kocaeli | Turkey | 41380 |
| 103 | Hacettepe University, School of Medicine | Ankara | Turkey | 06100 | |
| 104 | Ankara City Hospital | Ankara | Turkey | 06200 |
Sponsors and Collaborators
- PharmaMar
Investigators
- Principal Investigator: José Jimeno Doñaque, MD, PhD, PharmaMar
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- APL-D-003-20
- 2020-005951-19