Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2020-003936-25 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The objective of the study is to evaluate the efficacy and safety of two different doses of raloxifene orally administered compared to placebo in patients with early diagnosis of paucisymptomatic COVID-19.
Primary objectives:
Secondary objectives:
The study is a phase 2/3, multicenter, adaptive, randomized, placebo-controlled, double blind, parallel-group study to evaluate efficacy and safety of two doses of raloxifene in adult paucisymptomatic COVID-19 patients.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1: Raloxifene 60 mg | Experimental | After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing 60 mg of the active substance or placebo), a single daily oral dose of raloxifene 60 mg was administered; the treatment was taken by the patients for two weeks. |
|
| Group 2: Raloxifene 120 mg | Experimental | After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing 60 mg of the active substance or placebo), a single daily oral dose of raloxifene 120 mg was administered; the treatment was taken by the patients for two weeks. |
|
| Group 3: Placebo. | Placebo Comparator | After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing placebo), a single daily oral dose of placebo (2 capsules guarantee the blinding design) was administered; the treatment was taken by the patients for two weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Raloxifene | Drug | Raloxifene was administered as 60 mg hard gelatine capsule(s) once a day. Starting from day 2 of treatment: one single capsule (plus one of placebo to guarantee the blinding) containing 60 mg raloxifene was administered in Group 1, and 2 capsules 60 mg each for a total of 120 mg in Group 2. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Undetectable SARS-CoV-2 at PCR at Day 7 After Randomization in the FAS | Number of participants who, after an approved molecular test (PCR), were not detected as SARS-CoV2 positive. Based on Approved molecular test (PCR) result at day 7, the responses were considered as "detectable" if PCR result was "Positive" otherwise "undetectable" if PCR result was "Negative" . | At Day 7 |
| Number of Participants Not Requiring Oxygen Therapy and/or Mechanical Ventilation at Day 14 After Randomization in the FAS | Proportion of participants who does not require supplemental oxygen therapy (NEWS ≤ 2) and/or mechanical ventilation. NEWS is a system for scoring the physiological measurements that are routinely recorded at the patient's bedside. NEWS uses six physiological measurements. An additional two points are added if the patient is receiving oxygen therapy. The total possible score ranges from 0 to 20. If collected NEWS score > 2 or mechanical ventilation with result "Yes" then the response was considered as "Required". If collected NEWS score ≤ 2 and mechanical ventilation with result "No" then the response was considered as "Not Required" (if both NEWS score and mechanical ventilation were missing, patient was considered as missing). | At Day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Undetectable SARS-CoV-2 at PCR at Days 14 and 28 After Randomization in the FAS | Number of participants with undetectable SARS-CoV-2 at PCR at day 14 after randomization, and at day 28 after randomization. Based on Approved molecular test (PCR) result at days 14 and 28 after randomization, the responses were considered as "detectable" if PCR result was "Positive" otherwise "undetectable" if PCR result was "Negative". |
Not provided
Inclusion Criteria:
Subject autonomously provides informed consent prior to initiation of any study procedures
Males and females ≥ 40 years old
Understands and agrees to comply with planned study procedures, has the availability of an email address as well as an Internet connection at domicile location
Agrees to the collection of nasopharyngeal swabs and venous blood samples per protocol
Has laboratory-confirmed SARS-CoV-2 infection as determined by an approved molecular test (PCR) in Europe within 10 days at the screening time
Patient paucisymptomatic who complains at the screening time at least one of the following symptoms mild to moderate: fever, dyspnea, headache, cough, dysgeusia, conjunctivitis, vomiting, diarrhea, anosmia, muscle or body aches or other symptoms which in the opinion of the Investigator are part of the COVID-19 clinical picture
No need of supplemental oxygen therapy, mechanical ventilation
Females of child-bearing potential and with an active sexual life must not wish to get pregnant within 30 days after the end of the study and must be using at least one of the following reliable methods of contraception:
Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all female subjects, with child-bearing potential, pregnancy test result must be negative before first drug intake on T7 and T14.
Exclusion Criteria:
Being totally asymptomatic at the screening time
Requires supplemental oxygen therapy or mechanical ventilation
Being already under raloxifene or other SERM treatment for another medical condition at the time of randomization
Being concurrently involved in another trial with IP or participation in any clinical trial with IP for 1 months before this study. The 1-month interval is calculated as the time between the last visit of the previous study and the first day of the present study (date of the informed consent signature)
Clinically significant abnormal physical findings which could interfere with the objectives of the study
Diseases:
Autoimmune diseases receiving therapy at the time of randomization
Risk of venous thrombosis or any condition/disease that could bring to an extended period of immobilization
Ascertained or presumptive hypersensitivity to the active principles (raloxifene) and/or excipients or allergic reactions in general, which the Investigator considers may affect the outcome of the study
Medications: in particular cholestyramine (or any ion exchange resin), medications used in treatment of early or advanced breast cancer (including adjuvant therapy), warfarin, any drug that cannot be coadministered with the experimental compound
Pregnancy:
Women of childbearing potential and fertile men who does not agree to use at least one primary form of contraception for the duration of the study.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Francesco Sergio, MD, PhD | Dompé Farmaceutici | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Amiens | Amiens | France | ||||
| Clinique de l'infirmerie protestante de Lyon |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35582123 | Derived | Nicastri E, Marinangeli F, Pivetta E, Torri E, Reggiani F, Fiorentino G, Scorzolini L, Vettori S, Marsiglia C, Gavioli EM, Beccari AR, Terpolilli G, De Pizzol M, Goisis G, Mantelli F, Vaia F, Allegretti M; Raloxifene Territorial Health COVID19 STUDY GROUP. A phase 2 randomized, double-blinded, placebo-controlled, multicenter trial evaluating the efficacy and safety of raloxifene for patients with mild to moderate COVID-19. EClinicalMedicine. 2022 Jun;48:101450. doi: 10.1016/j.eclinm.2022.101450. Epub 2022 May 12. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Due to the premature study interruption, the sample size was smaller than that originally planned due to several reason that caused difficulties in patients enrolment.
Actual recruitment was greatly slower than expected and this determined a significant delay in study conduction, which in turn reflected on a study completion forecast that was not in line with Sponsor's planning.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Group 1: Raloxifene 60 mg | After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing 60 mg of the active substance or placebo), a single daily oral dose of raloxifene 60 mg was administered; the treatment was taken by the patients for two weeks. Raloxifene: Raloxifene was administered as 60 mg hard gelatine capsule(s) once a day. Starting from day 2 of treatment: one single capsule (plus one of placebo to guarantee the blinding) containing 60 mg raloxifene was administered in Group 1, and 2 capsules 60 mg each for a total of 120 mg in Group 2. |
| FG001 | Group 2: Raloxifene 120 mg | After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing 60 mg of the active substance or placebo), a single daily oral dose of raloxifene 120 mg was administered; the treatment was taken by the patients for two weeks. Raloxifene: Raloxifene was administered as 60 mg hard gelatine capsule(s) once a day. Starting from day 2 of treatment: one single capsule (plus one of placebo to guarantee the blinding) containing 60 mg raloxifene was administered in Group 1, and 2 capsules 60 mg each for a total of 120 mg in Group 2. |
| FG002 | Group 3: Placebo. | After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing placebo), a single daily oral dose of placebo (2 capsules guarantee the blinding design) was administered; the treatment was taken by the patients for two weeks. Placebo: Placebo was administered orally once a day as 2 capsules (for maintaining the blinding design) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The Full Analysis Set (FAS) population included all randomized patients who received at least one dose of the study medication. The FAS population was used for demographics, and primary and secondary efficacy analyses
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Raloxifene 60 mg (FAS) | After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing 60 mg of the active substance or placebo), a single daily oral dose of raloxifene 60 mg was administered; the treatment was taken by the patients for two weeks. Raloxifene: Raloxifene was administered as 60 mg hard gelatine capsule(s) once a day. Starting from day 2 of treatment: one single capsule (plus one of placebo to guarantee the blinding) containing 60 mg raloxifene was administered in Group 1, and 2 capsules 60 mg each for a total of 120 mg in Group 2. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Number of Participants With Undetectable SARS-CoV-2 at PCR at Day 7 After Randomization in the FAS | Number of participants who, after an approved molecular test (PCR), were not detected as SARS-CoV2 positive. Based on Approved molecular test (PCR) result at day 7, the responses were considered as "detectable" if PCR result was "Positive" otherwise "undetectable" if PCR result was "Negative" . | The Full Analysis Set (FAS) population included all randomized patients who received at least one dose of the study medication. The FAS population was used for primary and secondary efficacy analyses. | Posted | Count of Participants | Participants | At Day 7 |
|
The specific period of time over wich adverse events data were collected was within Day 7, 14 and 28 after randomization
An Adverse Event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Raloxifene 60 mg (SAF) | After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing 60 mg of the active substance or placebo), a single daily oral dose of raloxifene 60 mg was administered; the treatment was taken by the patients for two weeks. Raloxifene: Raloxifene was administered as 60 mg hard gelatine capsule(s) once a day. Starting from day 2 of treatment: one single capsule (plus one of placebo to guarantee the blinding) containing 60 mg raloxifene was administered in Group 1, and 2 capsules 60 mg each for a total of 120 mg in Group 2. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Development & Operations | Dompé Farmaceutici SpA | +39 02 583831 | clinical.trials@dompe.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 22, 2020 | May 4, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 7, 2021 | May 4, 2022 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D011014 | Pneumonia |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D020849 | Raloxifene Hydrochloride |
| ID | Term |
|---|---|
| D013629 | Tamoxifen |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
Not provided
Not provided
Multicenter, adaptive, double-blind, randomized, placebo controlled, double blind, parallelgroup, to study efficacy and safety, with the following adaptive components:
Not provided
Not provided
Appearance, including packaging and labelling, of the investigational medicinal product (IMP, capsules, packaging) will not allow to recognize actual treatment (either raloxifene or placebo).
|
| Placebo | Other | Placebo was administered orally once a day as 2 capsules (for maintaining the blinding design) |
|
|
| At days 14 and 28 after randomization |
| Number of Participants Not Requiring Oxygen Therapy and/or Mechanical Ventilation at Day 7 an d at Day 28 in the FAS | Proportion of participants who does not require supplemental oxygen therapy (NEWS ≤ 2) and/or mechanical ventilation after randomization; | At days 7 and 28 |
| Number of Patients in Each National Early Warning Score (NEWS) Category in the FAS | Proportion of patients in each National Early Warning Score (NEWS) category after randomization. NEWS is a system for scoring the physiological measurements that are routinely recorded at the patient's bedside. NEWS uses six physiological measurements: respiratory rate; oxygen saturation; temperature; systolic blood pressure; heart rate and level of consciousness. Each scores 0-3 and individual scores are added together for an overall score. An additional two points are added if the patient is receiving oxygen therapy. The total possible score ranges from 0 to 20. The higher the score, the worse the outcome. | At days 7, 14, 28 |
| Mean Value of National Early Warning Score (NEWS) Category in the FAS | Mean value of National Early Warning Score (NEWS) category after randomization. NEWS is a system for scoring the physiological measurements that are routinely recorded at the patient's bedside. The total possible score ranges from 0 to 20. The higher the score the greater the clinical risk. Higher scores indicate the need for escalation, medical review and possible clinical intervention and more intensive monitoring | At days 7, 14, 28 after randomization |
| Number of Hospitalized Participants Who at the Beginning of the Study Were at Domicile Isolation After Randomization in the FAS | Proportion of hospitalized participants at Day 7, Day 14 and Day 28 after randomization among subjects who at the beginning of the study were at domicile isolation. | At days 7, 14, 28 |
| Number of Participants Admitted to Intensive Care After Randomization in the FAS | Proportion of participants admitted to intensive care. Intensive care is a special medical treatment in which a patient who is dangerously ill is kept under constant observation, typically in a dedicated department of a hospital. | At days 7,14 ,28 |
| Number of Survivors in the FAS | Proportion of survivors after randomization. There were no events (i.e. deaths) in any treatment groups and thus the median overall survival could not be estimated. Overall survival was analysed according to the Kaplan-Meier method. Time to event curves were compared (i.e. comparisons of each active treatment group versus placebo) using log-rank test and estimates of hazard ratio were obtained using Cox proportional hazards model. | At days 7, 14, 28 |
| Quality of Life Questionnaire (EQ-5D-5L) at 3 Months After Randomization - EQ-5D Descriptive System | The EQ-5D-5L consists of: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the 5 dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the 5 dimensions can be combined into a 5-digit number describing the patient's health state. In the EQ VAS - quantitative measure of health outcome - the patient records a self-rates health on a vertical visual analogue scale (numbered from 0 to 100) which goes from 'Best imaginable health state' (100) to 'Worst imaginable health state' (0). | At month 3 After Randomization |
| Quality of Life Questionnaire (EQ-5D-5L) at 3 Months After Randomization - EQ VAS | The EQ-5D-5L consists of: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the 5 dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the 5 dimensions can be combined into a 5-digit number describing the patient's health state. In the EQ VAS - quantitative measure of health outcome - the patient records a self-rates health on a vertical visual analogue scale (numbered from 0 to 100) which goes from 'Best imaginable health state' (100) to 'Worst imaginable health state' (0). | At month 3 After Randomization |
| Caluire-et-Cuire |
| France |
| CH Emile Roux le Puy en Velay | Le Puy-en-Velay | France |
| Centre Hospitalier de Troyes | Troyes | France |
| Humanitas Gavazzeni | Bergamo | Italy |
| Ospedale San Salvatore | L’Aquila | Italy |
| AO dei Colli (Ospedale Monaldi) | Naples | Italy |
| INMI Lazzaro Spallanzani | Roma | Italy |
| Istituto Clinico Humanitas | Rozzano | Italy |
| A.O.U. Città della Salute e della Scienza | Torino | Italy |
| Hospital Universitario Virgen de la Victoria | Málaga | Spain |
| Other |
|
| BG001 | Raloxifene 120 mg (FAS) | After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing 60 mg of the active substance or placebo), a single daily oral dose of raloxifene 120 mg was administered; the treatment was taken by the patients for two weeks. Raloxifene: Raloxifene was administered as 60 mg hard gelatine capsule(s) once a day. Starting from day 2 of treatment: one single capsule (plus one of placebo to guarantee the blinding) containing 60 mg raloxifene was administered in Group 1, and 2 capsules 60 mg each for a total of 120 mg in Group 2. |
| BG002 | Placebo (FAS) | After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing placebo), a single daily oral dose of placebo (2 capsules guarantee the blinding design) was administered; the treatment was taken by the patients for two weeks. Placebo: Placebo was administered orally once a day as 2 capsules (for maintaining the blinding design) |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Raloxifene 120 mg | After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing 60 mg of the active substance or placebo), a single daily oral dose of raloxifene 120 mg was administered; the treatment was taken by the patients for two weeks. Raloxifene: Raloxifene was administered as 60 mg hard gelatine capsule(s) once a day. Starting from day 2 of treatment: one single capsule (plus one of placebo to guarantee the blinding) containing 60 mg raloxifene was administered in Group 1, and 2 capsules 60 mg each for a total of 120 mg in Group 2. |
| OG002 | Placebo | After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing placebo), a single daily oral dose of placebo (2 capsules guarantee the blinding design) was administered; the treatment was taken by the patients for two weeks. Placebo: Placebo was administered orally once a day as 2 capsules (for maintaining the blinding design) |
|
|
|
| Primary | Number of Participants Not Requiring Oxygen Therapy and/or Mechanical Ventilation at Day 14 After Randomization in the FAS | Proportion of participants who does not require supplemental oxygen therapy (NEWS ≤ 2) and/or mechanical ventilation. NEWS is a system for scoring the physiological measurements that are routinely recorded at the patient's bedside. NEWS uses six physiological measurements. An additional two points are added if the patient is receiving oxygen therapy. The total possible score ranges from 0 to 20. If collected NEWS score > 2 or mechanical ventilation with result "Yes" then the response was considered as "Required". If collected NEWS score ≤ 2 and mechanical ventilation with result "No" then the response was considered as "Not Required" (if both NEWS score and mechanical ventilation were missing, patient was considered as missing). | The Full Analysis Set (FAS) population included all randomized patients who received at least one dose of the study medication. The FAS population was used for primary and secondary efficacy analyses; | Posted | Count of Participants | Participants | At Day 14 |
|
|
|
|
| Secondary | Number of Participants With Undetectable SARS-CoV-2 at PCR at Days 14 and 28 After Randomization in the FAS | Number of participants with undetectable SARS-CoV-2 at PCR at day 14 after randomization, and at day 28 after randomization. Based on Approved molecular test (PCR) result at days 14 and 28 after randomization, the responses were considered as "detectable" if PCR result was "Positive" otherwise "undetectable" if PCR result was "Negative". | The Full Analysis Set (FAS) population included all randomized patients who received at least one dose of the study medication. The FAS population was used for primary and secondary efficacy analyses. | Posted | Count of Participants | Participants | At days 14 and 28 after randomization |
|
|
|
|
| Secondary | Number of Participants Not Requiring Oxygen Therapy and/or Mechanical Ventilation at Day 7 an d at Day 28 in the FAS | Proportion of participants who does not require supplemental oxygen therapy (NEWS ≤ 2) and/or mechanical ventilation after randomization; | The Full Analysis Set (FAS) population included all randomized patients who received at least one dose of the study medication. The FAS population was used for primary and secondary efficacy analyses; | Posted | Count of Participants | Participants | At days 7 and 28 |
|
|
|
|
| Secondary | Number of Patients in Each National Early Warning Score (NEWS) Category in the FAS | Proportion of patients in each National Early Warning Score (NEWS) category after randomization. NEWS is a system for scoring the physiological measurements that are routinely recorded at the patient's bedside. NEWS uses six physiological measurements: respiratory rate; oxygen saturation; temperature; systolic blood pressure; heart rate and level of consciousness. Each scores 0-3 and individual scores are added together for an overall score. An additional two points are added if the patient is receiving oxygen therapy. The total possible score ranges from 0 to 20. The higher the score, the worse the outcome. | The Full Analysis Set (FAS) population included all randomized patients who received at least one dose of the study medication. The FAS population was used for primary and secondary efficacy analyses; | Posted | Count of Participants | Participants | At days 7, 14, 28 |
|
|
|
| Secondary | Mean Value of National Early Warning Score (NEWS) Category in the FAS | Mean value of National Early Warning Score (NEWS) category after randomization. NEWS is a system for scoring the physiological measurements that are routinely recorded at the patient's bedside. The total possible score ranges from 0 to 20. The higher the score the greater the clinical risk. Higher scores indicate the need for escalation, medical review and possible clinical intervention and more intensive monitoring | The Full Analysis Set (FAS) population included all randomized patients who received at least one dose of the study medication. The FAS population was used for primary and secondary efficacy analyses; | Posted | Mean | Standard Deviation | score on a scale | At days 7, 14, 28 after randomization |
|
|
|
| Secondary | Number of Hospitalized Participants Who at the Beginning of the Study Were at Domicile Isolation After Randomization in the FAS | Proportion of hospitalized participants at Day 7, Day 14 and Day 28 after randomization among subjects who at the beginning of the study were at domicile isolation. | The Full Analysis Set (FAS) population included all randomized patients who received at least one dose of the study medication. The FAS population was used for primary and secondary efficacy analyses; | Posted | Count of Participants | Participants | At days 7, 14, 28 |
|
|
|
|
| Secondary | Number of Participants Admitted to Intensive Care After Randomization in the FAS | Proportion of participants admitted to intensive care. Intensive care is a special medical treatment in which a patient who is dangerously ill is kept under constant observation, typically in a dedicated department of a hospital. | The Full Analysis Set (FAS) population included all randomized patients who received at least one dose of the study medication. The FAS population was used for primary and secondary efficacy analyses. | Posted | Count of Participants | Participants | At days 7,14 ,28 |
|
|
|
| Secondary | Number of Survivors in the FAS | Proportion of survivors after randomization. There were no events (i.e. deaths) in any treatment groups and thus the median overall survival could not be estimated. Overall survival was analysed according to the Kaplan-Meier method. Time to event curves were compared (i.e. comparisons of each active treatment group versus placebo) using log-rank test and estimates of hazard ratio were obtained using Cox proportional hazards model. | The Full Analysis Set (FAS) population included all randomized patients who received at least one dose of the study medication. The FAS population was used for primary and secondary efficacy analyses. | Posted | Count of Participants | Participants | At days 7, 14, 28 |
|
|
|
|
| Secondary | Quality of Life Questionnaire (EQ-5D-5L) at 3 Months After Randomization - EQ-5D Descriptive System | The EQ-5D-5L consists of: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the 5 dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the 5 dimensions can be combined into a 5-digit number describing the patient's health state. In the EQ VAS - quantitative measure of health outcome - the patient records a self-rates health on a vertical visual analogue scale (numbered from 0 to 100) which goes from 'Best imaginable health state' (100) to 'Worst imaginable health state' (0). | The Full Analysis Set (FAS) population included all randomized patients who received at least one dose of the study medication. The FAS population was used for primary and secondary efficacy analyses; | Posted | Count of Participants | Participants | At month 3 After Randomization |
|
|
|
| Secondary | Quality of Life Questionnaire (EQ-5D-5L) at 3 Months After Randomization - EQ VAS | The EQ-5D-5L consists of: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the 5 dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the 5 dimensions can be combined into a 5-digit number describing the patient's health state. In the EQ VAS - quantitative measure of health outcome - the patient records a self-rates health on a vertical visual analogue scale (numbered from 0 to 100) which goes from 'Best imaginable health state' (100) to 'Worst imaginable health state' (0). | The Full Analysis Set (FAS) population included all randomized patients who received at least one dose of the study medication. The FAS population was used for primary and secondary efficacy analyses; | Posted | Mean | Standard Deviation | score on a scale | At month 3 After Randomization |
|
|
|
| 0 |
| 22 |
| 3 |
| 22 |
| 6 |
| 22 |
| EG001 | Raloxifene 120 mg (SAF) | After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing 60 mg of the active substance or placebo), a single daily oral dose of raloxifene 120 mg was administered; the treatment was taken by the patients for two weeks. Raloxifene: Raloxifene was administered as 60 mg hard gelatine capsule(s) once a day. Starting from day 2 of treatment: one single capsule (plus one of placebo to guarantee the blinding) containing 60 mg raloxifene was administered in Group 1, and 2 capsules 60 mg each for a total of 120 mg in Group 2. | 0 | 20 | 2 | 20 | 8 | 20 |
| EG002 | Placebo (SAF) | After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing placebo), a single daily oral dose of placebo (2 capsules guarantee the blinding design) was administered; the treatment was taken by the patients for two weeks. Placebo: Placebo was administered orally once a day as 2 capsules (for maintaining the blinding design) | 0 | 19 | 5 | 19 | 6 | 19 |
| Pyrexia | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Covid-19 pneumonia | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
| Haemangioma of liver | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Gastric disorder | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Vessel puncture site bruise | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Cholestasis | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hepatitis | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
|
| COVID-19 pneumonia | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
| Chest injury | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
|
| Fibrin D dimer increased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Lipids increased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Pareaesthesia | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
|
| Postmenopausal haemorrage | Reproductive system and breast disorders | MedDRA 23.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
|
Not provided
Not provided
| D018352 |
| Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| >0.999 |
| Odds Ratio (OR) |
| 0.963 |
| 2-Sided |
| 95 |
| 0.185 |
| 4.977 |
| Superiority |
Analysis is based on Exact Binary logistic regression model with treatment group, age group and status as main effects |
| This sensitivity analysis is conducted on the per protocol (PP) population: n=18 in the Raloxifene 60 mg arm; n=17 in the Raloxifene 120 mg arm; and n=17 in the Placebo arm | Regression, Logistic | 0.5378 | Analysis is based on Exact Binary logistic regression model with treatment group, age group and status as main effects. | Odds Ratio (OR) | 2.340 | 2-Sided | 95 | 0.350 | 20.153 | Superiority |
| This sensitivity analysis is conducted on the per protocol (PP) population: n=18 in the Raloxifene 60 mg arm; n=17 in the Raloxifene 120 mg arm; and n=17 in the Placebo arm | Regression, Logistic | >0.999 | Analysis is based on Exact Binary logistic regression model with treatment group, age group and status as main effects. | Odds Ratio (OR) | 1.209 | 2-Sided | 95 | 0.185 | 8.589 | Superiority |
| Title | Measurements |
|---|---|
|
At day 14
| Regression, Logistic |
Analysis is based on Exact Binary logistic regression model with treatment group, age group and status as main effects. |
| 0.2553 |
| Odds Ratio (OR) |
| 3.202 |
| 2-Sided |
| 95 |
| 0.541 |
| 22.116 |
| Superiority |
| at Day 28 | Regression, Logistic | Analysis is based on Exact Binary logistic regression model with treatment group, age group and status as main effects. | 0.6189 | Odds Ratio (OR) | 2.160 | 2-Sided | 95 | 0.294 | 18.532 | Superiority |
| at Day 28 | Regression, Logistic | Analysis is based on Exact Binary logistic regression model with treatment group, age group and status as main effects. | 0.1662 | Odds Ratio (OR) | 7.220 | 2-Sided | 95 | 0.586 | 413.499 | Superiority |
| Title | Measurements |
|---|---|
|
at Day 7
| Regression, Logistic |
Analysis is based on Exact Binary logistic regression model with treatment group, age group and status as main effects |
| >0.999 |
| Odds Ratio (OR) |
| 1.156 |
| 2-Sided |
| 95 |
| 0.200 |
| 6.822 |
| Superiority |
| at Day 28 | Regression, Logistic | Analysis is based on Exact Binary logistic regression model with treatment group, age group and status as main effects | >0.999 | Odds Ratio (OR) | 1.066 | 2-Sided | 95 | 0.208 | 5.478 | Superiority |
| at Day 28 | Regression, Logistic | Analysis is based on Exact Binary logistic regression model with treatment group, age group and status as main effects | 0.5465 | Odds Ratio (OR) | 2.068 | 2-Sided | 95 | 0.369 | 12.580 | Superiority |
| Title | Measurements |
|---|---|
|
| Day 7 - Score 2 |
|
| Day 7 - Score 3 |
|
| Day 7 - Score 4 |
|
| Day 7 - Score 5 |
|
| Day 7 - Score 7 |
|
| Day 7 - Missing |
|
| Day 14 - Score 0 |
|
| Day 14 - Score 1 |
|
| Day 14 - Score 2 |
|
| Day 14 - Score 3 |
|
| Day 14 - Score 4 |
|
| Day 14 - Score 5 |
|
| Day 14 - Score 6 |
|
| Day 14 - Missing |
|
| Day 28 - Score 0 |
|
| Day 28 - Score 1 |
|
| Day 28 - Score 2 |
|
| Day 28 - Score 3 |
|
| Day 28 - Score 4 |
|
| Day 28 - Missing |
|
| Day 14 |
|
|
| Day 28 |
|
|
| Title | Measurements |
|---|---|
|
| Day 28 |
|
| The proportion of hospitalized participants who at the beginning of the study were at domicile isolation at Day 7, Day 14 and Day 28 after randomization was analysed using comparison of proportions (i.e. comparisons of each active treatment group versus placebo at each assessment day) through Fisher's exact test and was summarized using frequency and percent by treatment and visit. Herein Day 7 R120 vs placebo | Fisher Exact | 0.4075 | P-Value comparing % among treatment groups Raloxifene 120 mg versus Placebo using Fisher's Exact test. | Superiority |
| The proportion of hospitalized participants who at the beginning of the study were at domicile isolation at Day 7, Day 14 and Day 28 after randomization was analysed using comparison of proportions (i.e. comparisons of each active treatment group versus placebo at each assessment day) through Fisher's exact test and was summarized using frequency and percent by treatment and visit. Herein Day 14 R60 vs placebo | Fisher Exact | 0.3899 | P-Value comparing % among treatment groups Raloxifene 60mg versus Placebo using Fisher's Exact test. | Superiority |
| The proportion of hospitalized participants who at the beginning of the study were at domicile isolation at Day 7, Day 14 and Day 28 after randomization was analysed using comparison of proportions (i.e. comparisons of each active treatment group versus placebo at each assessment day) through Fisher's exact test and was summarized using frequency and percent by treatment and visit. Herein Day 14 R120 vs placebo | Fisher Exact | P-Value comparing % among treatment groups Raloxifene 120mg versus Placebo using Fisher's Exact test. | 0.4075 | Superiority |
| The proportion of hospitalized participants who at the beginning of the study were at domicile isolation at Day 7, Day 14 and Day 28 after randomization was analysed using comparison of proportions (i.e. comparisons of each active treatment group versus placebo at each assessment day) through Fisher's exact test and was summarized using frequency and percent by treatment and visit. Herein Day 28 R60 vs placebo | Fisher Exact | 0.6846 | P-Value comparing % among treatment groups Raloxifene 60mg versus Placebo using Fisher's Exact test. | Superiority |
| The proportion of hospitalized participants who at the beginning of the study were at domicile isolation at Day 7, Day 14 and Day 28 after randomization was analysed using comparison of proportions (i.e. comparisons of each active treatment group versus placebo at each assessment day) through Fisher's exact test and was summarized using frequency and percent by treatment and visit. Herein Day 28 R120 vs placebo | Fisher Exact | 0.6614 | P-Value comparing % among treatment groups Raloxifene 120mg versus Placebo using Fisher's Exact test. | Superiority |
| Title | Measurements |
|---|---|
|
| Day 28 |
|
p value= not estimable
| Hazard Ratio (HR) |
| 1.00 |
| 2-Sided |
| 95 |
| 1.00 |
| 1.00 |
| Superiority |
|
| mobility - moderate problems in walking about |
|
| mobility-severe problems in walking about |
|
| mobility - unable to walk about |
|
| self care - no problems washing or dressing myself |
|
| self care - slight problems washing or dressing myself |
|
| self care - moderate problems washing or dressing myself |
|
| self care - severe problems washing or dressing myself |
|
| self care - unable to wash or dress myself |
|
| usual activities - no problems doing my usual activities |
|
| usual activities - slight problems doing my usual activities |
|
| usual activities - moderate problems doing my usual activities |
|
| usual activities - severe problems doing my usual activities |
|
| usual activities - unable to do my usual activities |
|
| Pain/discomfort - no pain or discomfort |
|
| Pain/discomfort - slight pain or discomfort |
|
| Pain/discomfort - moderate pain or discomfort |
|
| Pain/discomfort - severe pain or discomfort |
|
| Pain/discomfort - extreme pain or discomfort |
|
| Anxiety / Depression - I am not anxious or depressed |
|
| Anxiety / Depression - I am slightly anxious or depressed |
|
| Anxiety / Depression - I am moderately anxious or depressed |
|
| Anxiety / Depression - I am severely anxious or depressed |
|
| Anxiety / Depression - I am extremely anxious or depressed |
|