Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
226
Countries
1
Sites
5
Cytomegalovirus in high-risk immunocompetent major heart surgery.
To determine the clinical impact of administering targeted pre-emptive antiviral therapy to high-risk (≥3 days in the cardiac surgery ICU and CMV viral load), immunocompetent adults, after MHS.
Key facts
- Sponsor
- Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Virus Diseases [C02]
- Trial duration
- 19 Sep 2023 → 7 Jul 2025
- Decision date (initial)
- 2023-01-10
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Instituto de Salud Carlos III (ISCIII)
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
To determine the clinical impact of administering targeted pre-emptive antiviral therapy to high-risk (≥3 days in the cardiac surgery ICU and CMV viral load), immunocompetent adults, after MHS.
Secondary objectives 6
- To evaluate Quantiferon-CMV and other immunological markers prognosis impact to determine the presence of viremia and persistent viremia in this population.
- To evaluate the possible alterations of innate and acquired immunity that occur in the immediate post-operative period and their ability to predict the development of CMV infection.
- To evaluate the differences, if found, in basic immunological parameters that could explain different outcomes beyond the effect of antiviral therapy.
- To identify the possible association of the viral load negativization with immunomodulation in some of the components associated with the CMV immune response in those patients treated with antiviral therapy.
- To assess the impact of plasma serum concentrations of antiviral therapy on outcomes and toxicity (exclusive for PK substudy population).
- To evaluate the antiviral drugs safety.
Conditions and MedDRA coding
Cytomegalovirus in high-risk immunocompetent major heart surgery.
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Screening period. The screening period will last approximately 3-90 days, since MHS to the inclusion visit (v1). Once the patients have overcome the surgery, those eligible for participating in the study, will be enrolled.
|
Randomised Controlled | Double | [{"id":32853,"code":3,"name":"Monitor"},{"id":32852,"code":2,"name":"Investigator"},{"id":32851,"code":1,"name":"Subject"}] | |
| 2 | Epoch 1. After subjects are determined to be eligible according to the inclusion/exclusion criteria, they are recruited into study epoch 1. In this period, the subjects will be tested to determine the CMV DNA viral load by a PCR test (v1). All positive patients (CMV viral load ≥100UI/ml) will enter the epoch 2 of the study. Negative patients (CMV viral load <100UI/ml) will be tested weekly until they become positive or until the hospital discharge. Those negative patients at discharge will only participate in this period, serving as a negative control to the comparison analysis.
|
Randomised Controlled | Double | [{"id":32855,"code":3,"name":"Monitor"},{"id":32857,"code":2,"name":"Investigator"},{"id":32856,"code":1,"name":"Subject"}] | |
| 3 | Epoch 2. This epoch consists in 6 visits (v1, v2, v3, v4, v5 and v6). Positive patients will be randomized to ganciclovir/valganciclovir or placebo (1:1) and treated for 14 days. Furthermore, a security 28-days follow up will be done for all patients participating in this epoch, starting from enrolment to the end of study.
|
Randomised Controlled | Double | [{"id":32860,"code":1,"name":"Subject"},{"id":32859,"code":3,"name":"Monitor"},{"id":32861,"code":2,"name":"Investigator"}] | Investigational arm (antiviral therapy): IV ganciclovir or the equivalent oral valganciclovir.: Patients will be assigned to one of 2 treatment arms in a ratio of 1:1 Control arm: Placebo: Patients will be assigned to one of the 2 treatment arms in a ratio of 1:1 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- Written informed consent must be obtained before any study-specific assessment is performed.
- Adult patients (≥18 years old).
- Patients that underwent a MHS in the last 90 days prior to inclusion.
- Patients remaining in the ICU at least 72h after the surgery.
- Female patients of child-bearing potential must have a negative urine pregnancy test at screening and agree to use reliable methods of contraception upon enrolment according to the recommendations provided by CTFG, during the treatment period and for one month following the last dose of investigational drug.
- Male patients must use a reliable method of contraception (if sexually active with a female of child-bearing potential) upon enrolment according to the recommendations provided by CTFG, during the treatment period, and for 3 months following the last dose of investigational drug.
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Exclusion criteria 6
- Immunocompromised patients: HIV positive infection, Neutropenia (neutrophile count <1000/mm3), Platelet count <25,000 U/µL, Hematopoietic transplant, Solid organ transplant needing immunosuppression, Chemotherapy received in the last 3 months prior to inclusion, Hereditary immunosuppression, Immunomodulatory drugs treatment (TNFα or rituximab) in the prior 3 months or alemtuzumab in the previous 6 months, Oral or intravenous (IV) corticosteroids treatment (>10 mg/day) in the last 30 days, Methotrexate treatment (≥10 mg/s) or azathioprine treatment (≥75 mg/s).
- Females who are pregnant or breastfeeding.
- Patients treated with antiviral drugs that are active towards CMV, such as, ganciclovir, valganciclovir, acyclovir, valacyclovir, famciclovir, cidofovir, letermovir, maribavir, brincidofovir) in the last week before inclusion.
- Patients participating in another clinical trial with an experimental drug.
- Patients whose life expectancy is 48-72h.
- Patients with known hypersensitivity to valganciclovir, ganciclovir or any of the excipients.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Number of days of good outcome during the 30 days follow-up. A good outcome implies that the patient is alive, out of the ICU, with no systemic antimicrobials, no mechanical ventilation, and no SAEs.
Secondary endpoints 6
- Predictive value (specificity, sensibility, cut-off point and area under the curve [AUC]) of Quantiferon-CMV and other immunological markers (total lymphocyte count, CD4/CD8, NK cells, IL-6 and IL-8 levels, serum Immunoglobulin levels) in prediction the presence of viremia.
- Description of immunologic parameters and their ability (specificity, sensibility, cut-off point and AUC) to predict the development of CM infection.
- Comparation of immunological parameters between investigational and placebo groups at inclusion (day 0), end of treatment (day 14) and end of study (day 30).
- Quantification of the following variables: total lymphocyte count, CD4/CD8, NK cells, IL-6 and IL-8 levels, serum Immunoglobulin levels and its correlation with the viral load.
- Quantification of Cmin and Cmax (CMV peak and trough viral load in blood) and their correlation with toxicity (AE, SAEs, etc.) Exclusive for PK substudy population.
- Number of grade 3 or higher AEs related to antiviral drugs.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
SUB07881MIG · Substance
- Active substance
- Ganciclovir
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 10 mg/Kg milligram(s)/kilogram
- Max total dose
- 140 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB00007MIG · Substance
- Active substance
- Valganciclovir
- Pharmaceutical form
- POWDER FOR ORAL SOLUTION
- Route of administration
- ORAL USE
- Max daily dose
- 1800 mg milligram(s)
- Max total dose
- 25200 mg milligram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 2
Physiological saline: solution for itravenous infusion use.
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon
- Sponsor organisation
- Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon
- Address
- Calle Doctor Esquerdo 46
- City
- Madrid
- Postcode
- 28007
- Country
- Spain
Scientific contact point
- Organisation
- Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon
- Contact name
- FIBHGM
Public contact point
- Organisation
- Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon
- Contact name
- FIBHGM
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Dynamic Science S.L. ORG-100041907
|
Barcelona, Spain | On site monitoring, Code 10, Code 11, Code 12, Code 5, Data management, E-data capture, Code 8 |
Locations
1 EU/EEA country · 5 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Ended | 226 | 5 |
| Rest of world | — | 0 | — |
Investigational sites
Complexo Hospitalario Universitario De Vigo
Anesthesiology, Estrada Clara Campoamor N 341, 36312, Vigo
Hospital General Universitario Gregorio Maranon
Microbiology, Calle Del Doctor Esquerdo 46, 28009, Madrid
Hospital Universitario Marques De Valdecilla
Infectious Diseases, 5 Planta, Avenida Valdecilla S/n, Santander
Hospital Universitario Ramon Y Cajal
Infectious Diseases, Carretera Del Colmenar Viejo Km 9 100, Por El Pardo, Madrid
Hospital Universitario Central De Asturias
Cardiovascular surgery, Avenida De Roma S/n, 33011, Oviedo
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Spain | 2023-09-19 | 2023-11-29 | 2025-06-01 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2022-09-15 | Spain | Acceptable 2023-01-04
|
2023-01-10 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-04-28 | Spain | Acceptable 2023-06-06
|
2023-06-19 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2023-11-23 | Spain | Acceptable | 2023-12-20 |