## Protocol Section
### Identification Module
**NCT ID:** NCT06418048

**Acronym:** INDI-REBIO

**Brief Title:** INfectious DIsease REgistry BIObank

**Official Title:** Prospective Registry and Biobank of Patients With Infectious Diseases

#### Organization Study ID Info
**ID:** CET 138-2023
#### Organization
**Class:** OTHER
**Full Name:** IRCCS San Raffaele
### Status Module
#### Completion Date
**Date:** 2044-07-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-13

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2044-01-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-02-01

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-01-31
**Study First Submit QC Date:** 2024-05-13
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** IRCCS San Raffaele

#### Responsible Party

**Investigator Affiliation:** Ospedale San Raffaele

**Investigator Full Name:** Castagna Antonella

**Investigator Title:** Full Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Prospective observational study designed to describe the clinical, laboratory, imaging, microbiological characteristics and treatment of specific infectious diseases, with the addition of a dedicated biobank.

**Detailed Description:** The registry would provide a comprehensive database including a vast population of patients with infectious diseases, favoring the analysis of clinical, laboratory and therapeutic data of specific infectious conditions.

Specific infectious diseases of major interest include, among others:

* Bloodstream infections (i.e.: infectious syndromes manifesting with bacteremia)
* Endovascular infections (i.e.: infective endocarditis, cardiovascular implantable electronic device infections, vascular graft infections, etc.)
* Central nervous system infections (i.e.: meningitis, encephalitis, cerebral abscess, ventricular shunts infections, etc.)
* Bone and joint infections (i.e.: osteomyelitis, spondylodiscitis, prosthetic joint infections, etc.)
* Sexually transmitted infections (i.e.: gonococcal and non-gonococcal urethritis, proctitis, epididymo-orchitis, syphilis, etc.)
* HIV infection
* Emerging and re-emerging infectious diseases.

General objectives of the study for each specific infectious disease include:

* description and evolution over time of clinical and laboratory characteristics of patients with specific infectious diseases;
* description and evolution over time of microbial isolates, including antimicrobial susceptibility testing;
* description and evolution over time of treatment employed in patients with specific infectious diseases;
* evaluation of predictive factors for treatment success and mortality in patients with specific infectious diseases;
* description, evaluation and prognostic impact of microbial, immunological and inflammatory biomarkers.

The general study objectives, along with more specific objectives related to a specific infectious disease, will be evaluated in specific observational studies, nested within the Registry (i.e., using data and biosamples collected in the Registry with the potential addition of data obtained from investigations performed on available biological samples).

To achieve these objectives, participants are asked to donate biological samples (blood, cerebrospinal fluid, urine, other relevant biological samples related to the specific infectious disease, collected according to good clinical practice and available guidelines) for studies to identify modifiers of a specific infectious disease and to establish and validate biological markers tracking the progressive course of the considered disease, along with drug efficacy and toxicity.

The following clinical and laboratory data will be recorded at baseline and at follow-up visits:

* Age, measured in years
* Sex at birth (male, female)
* Comorbidities, measured with Charlson score (minimum 0 - maximum 37; higher scores linked to worse outcome)
* Source of infection, (central nervous system, respiratory tract, endovascular infection, intra-abdominal, urinary tract, skin and soft tissue, bone and joint, other).
* Sequential Organ Failure Assessment (SOFA) score (minimum 0 - maximum 24; higher scores linked to worse outcome)
* Pitt Score (minum 0 - maximum 14; higher scores linked to worse outcome)
* Length of hospital stay (days)
* Number of patients requiring Intensive care unit (ICU) admission, surgical interventions or other procedures
* Nerological impairment (Rankin scale \[minimum 0 - maximum 6; higher scores linked to worse outcome\])
* Functional impairment (Karnofsky scale \[minum 0 - maximum 100; higher scores linked to better outcome\])
* Results of routine laboratory tests
* Drug plasma concentrations
* Results of microbiological investigations (identification of the causative organisms, antimicrobial susceptibility testing results, mechanism of resistance)
* Results of imaging investigations
* Treatment strategies (type, dose, administration of antimicrobials)
* Development of drug toxicities
* Mortality (all-cause and infection-attributable)

Both data and biosamples will be collected starting from the baseline (BL) of the infectious disease after obtaining informed consent. Follow-up data and biosamples will be collected at the end of treatment (EOT) and at 6 months after the EOT for the specific condition or, in case of no therapeutic intervention, at 6 months after diagnosis. In patients with HIV infection follow-up data and biosamples will be collected yearly after baseline. Additional data and biosamples will be collected at other time-points according to the usual temporal evolution of specific diseases, and in case of relevant clinical events or therapeutic modification. All specimens will be collected according to good clinical practice and available national and international guidelines.

Data analysis will be performed by the investigators on approved proposals. Statistical methods will be defined as part of the proposals.

The variables of the study will be described using means or medians and 95% confidence intervals or interquartile ranges for continuous variables and proportions with their 95% confidence intervals for categorical variables.

Comparisons between groups will be made using the chi-square test or Fisher's exact test (categorical variables) or using the non-parametric Mann-Whitney test (continuous variables).

Significant variations in continuous variables over time may be assessed using t-tests for paired data o Wilcoxon ranks sign test (only two timepoints) o analysis of variance for repeated measures or linear mixed models (all timepoints available during follow-up).

The presence of linear relationships between continuous variables can be tested by means of Pearson correlation coefficients (parametric) or Spearman correlation coefficients (non-parametric).

Logistic regression models will be applied to determine the predictors of outcomes; the risks (odds ratios) and the corresponding 95% confidence intervals will be reported.

Cox regression models will be applied to determine predictors of outcomes; risks (odds ratios) and corresponding 95% confidence intervals will be reported.

### Conditions Module

**Conditions:**

- Bloodstream Infections

- Central Nervous System Infections

- Bone and Joint Infections

- Endovascular Infections

- Infective Endocarditis

- CIED-related Infections

- Vertebral Osteomyelitis

### Design Module

#### Bio Spec

**Description:** * Blood
* Cerebrospinal fluid (CSF)
* Respiratory specimens
* Synovial fluid
* Urine
* Stool
* Seminal fluid
* Tissue samples
* Microbial isolates

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 10000

**Type:** ESTIMATED

**Patient Registry:** True

**Study Type:** OBSERVATIONAL

**Target Duration:** 20 Years

### Outcomes Module

#### Primary Outcomes

**Description:** Describe the clinical presentation of specific infectious diseases, by means of Sequential Organ Failure Assessment (SOFA) score (minimum 0 - maximum 24; higher scores linked to worse outcome).

**Measure:** Clinical characteristics of specific infectious diseases

**Time Frame:** 6 months (with the exception of people living with HIV)

**Description:** Describe the microbiological characteristics of specific infectious diseases. Specifically:

* Identification of the causative organisms
* Antimicrobial susceptibility testing results
* Mechanism of resistance

**Measure:** Microbiological characteristics of specific infectious diseases

**Time Frame:** 6 months (with the exception of people living with HIV)

**Description:** Describe the antimicrobial treatment of specific infectious diseases

**Measure:** Treatment of specific infectious diseases

**Time Frame:** 6 months (with the exception of people living with HIV)

#### Secondary Outcomes

**Description:** Describe the predictive factors of microbiological cure, defined as negativization of cultures from the infected site

**Measure:** Predictive factors of microbiological cure

**Time Frame:** 6 months (with the exception of people living with HIV)

**Description:** Describe the predictive factors of clinical cure, defined as resolution of symptoms and signs attributable to the specific infectious disease

**Measure:** Predictive factors of clinical cure

**Time Frame:** 6 months (with the exception of people living with HIV)

**Description:** Describe the number of patients needing surgical intervention or other procedures

**Measure:** Need for surgical intervention or other procedures

**Time Frame:** 6 months (with the exception of people living with HIV)

**Description:** Describe the number of patients needing ICU transfer

**Measure:** Need for ICU

**Time Frame:** 6 months (with the exception of people living with HIV)

**Description:** Describe mortality due to any cause

**Measure:** Overall mortality

**Time Frame:** 6 months (with the exception of people living with HIV)

**Description:** Describe mortality due to the specific infectious disease

**Measure:** Infection-attributable mortality

**Time Frame:** 6 months (with the exception of people living with HIV)

**Description:** Describe the extent of neurological impairment (Rankin scale \[minimum 0 - maximum 6; higher scores linked to worse outcome\])

**Measure:** Neurological impairment

**Time Frame:** 6 months (with the exception of people living with HIV)

**Description:** Describe the extent of functional impairment (Karnofsky scale \[minum 0 - maximum 100; higher scores linked to better outcome\])

**Measure:** Functional impairment

**Time Frame:** 6 months (with the exception of people living with HIV)

**Description:** Describe the development of comorbidities (e.g. diabetes, cardiovascular diseases, etc.)

**Measure:** Development of comorbidities

**Time Frame:** 6 months (with the exception of people living with HIV)

**Description:** Describe the development of drug toxicities. Specifically, but not limited to:

* Nephrotoxicity, measured with serum creatinine levels (milligrams per deciliter)
* Hepatotoxicity, measured with alanine aminotransferase and aspartate aminostrasferase (units per liter), bilirubin (milligrams per deciliter), prothrombin time (seconds)
* Hematological Toxicity, measured with complete blood cell count (cells per microliter), hemoglobin (grams per deciliter), platelets (count per microliter)
* Cardiotoxicity, evaluated with electrocardiogram monitoring for arrhythmias
* Neurotoxicity, measured with Rankin scale (minimum 0 - maximum 6; higher scores linked to worse outcome)
* Gastrointestinal Toxicity, measured with Bristol stool chart

**Measure:** Development of drug toxicity

**Time Frame:** 6 months (with the exception of people living with HIV)

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Patients with clinically suspected or microbiologically documented infectious diseases (bacterial, viral, fungal or parasitic);
* At least 18 years of age or older;
* Able to provide informed consent;
* Participants who are unable to understand the study protocol or are unable to give informed consent, but have a legal representative

Exclusion Criteria:

- Participants who are unable to understand the study protocol or are unable to give informed consent, and have no legal representative.

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Patients with specific infectious diseases followed at the IRCCS San Raffaele Hospital (either as inpatients or outpatients).

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** carini.elisabetta@hsr.it

**Name:** Elisabetta Carini

**Phone:** +390226437934

**Role:** CONTACT

**Contact 2:**

**Email:** bagaglio.sabrina@hsr.it

**Name:** Sabrina Bagaglio

**Phone:** +390226432276

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Milan

**Contacts:**

***Contact 1:***

- **Email:** carini.elisabetta@hsr.it

- **Name:** Elisabetta Carini

- **Phone:** +390226437934

- **Role:** CONTACT

**Country:** Italy

**Facility:** San Raffaele Scientific Institute

**Status:** RECRUITING

#### Overall Officials

**Official 1:**

**Affiliation:** IRCCS San Raffaele Scientific Institute

**Name:** Marco Ripa, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

- ID: D000006331

- Term: Heart Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000018746

- Term: Systemic Inflammatory Response Syndrome

- ID: D000007249

- Term: Inflammation

- ID: D000001850

- Term: Bone Diseases, Infectious

- ID: D000001847

- Term: Bone Diseases

- ID: D000009140

- Term: Musculoskeletal Diseases

- ID: D000001424

- Term: Bacterial Infections

- ID: D000001423

- Term: Bacterial Infections and Mycoses

- ID: D000053821

- Term: Cardiovascular Infections

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: All

- Name: All Conditions

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10283

- Name: Infections

- Relevance: HIGH

- As Found: Infection

- ID: M7859

- Name: Endocarditis, Bacterial

- Relevance: HIGH

- As Found: Infective Endocarditis

- ID: M7858

- Name: Endocarditis

- Relevance: HIGH

- As Found: Infective Endocarditis

- ID: M6368

- Name: Communicable Diseases

- Relevance: HIGH

- As Found: Infection

- ID: M20864

- Name: Sepsis

- Relevance: HIGH

- As Found: Bloodstream Infection

- ID: M12942

- Name: Osteomyelitis

- Relevance: HIGH

- As Found: Osteomyelitis

- ID: M5743

- Name: Central Nervous System Infections

- Relevance: HIGH

- As Found: Central Nervous System Infections

- ID: M16869

- Name: Toxemia

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: M9419

- Name: Heart Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M20818

- Name: Systemic Inflammatory Response Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M10293

- Name: Inflammation

- Relevance: LOW

- As Found: Unknown

- ID: M5126

- Name: Bone Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5129

- Name: Bone Diseases, Infectious

- Relevance: LOW

- As Found: Unknown

- ID: M12097

- Name: Musculoskeletal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M4722

- Name: Bacterial Infections

- Relevance: LOW

- As Found: Unknown

- ID: M12136

- Name: Mycoses

- Relevance: LOW

- As Found: Unknown

- ID: M4721

- Name: Bacterial Infections and Mycoses

- Relevance: LOW

- As Found: Unknown

- ID: M27489

- Name: Cardiovascular Infections

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3065

- Name: Infective Endocarditis

- Relevance: HIGH

- As Found: Infective Endocarditis

- ID: T4321

- Name: Osteomyelitis

- Relevance: HIGH

- As Found: Osteomyelitis

### Condition Browse Module - Meshes

- ID: D000007239

- Term: Infections

- ID: D000003141

- Term: Communicable Diseases

- ID: D000018805

- Term: Sepsis

- ID: D000010019

- Term: Osteomyelitis

- ID: D000004697

- Term: Endocarditis, Bacterial

- ID: D000002494

- Term: Central Nervous System Infections

- ID: D000004696

- Term: Endocarditis

### Misc Info Module

- Version Holder: 2024-05-31
