Treatment of Adenovirus Disseminated Infections in Hematopoietic Stem Cell Transplant Patients With Adenovirus Digestive Replication

• Conditions: Patients Who Underwent Allograft

• Registration Number: NCT03481244
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Disseminated Adv infections are associated with high morbidity and mortality in HSCT pediatric patients. The most common source of Adv infection after pediatric HSCT is the host digestive tract where latent Adv are reactivated after engraftment. We have shown in a monocentric study that Adv viral load in stools is a predictive factor of blood infection in children with digestive Adv infections. We assume that an early treatment, with antiviral drugs, such as cidofovir and brincidofovir, may avoid severe Adv infections and diseases and thus that molecular surveillance in stool is a critical factor for the control of Adv reactivations.

The study has two main objectives: (i) confirming the impact of Adv viral load in stools on the occurrence of blood infection based on a multicentric prospective cohort study design; and (ii) determining the prognostic and predictive factors for efficacy and toxicity of antiviral drugs, such as brincidofovir and cidofovir.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-03-22
• Study First Submitted QC: 2018-03-27
• Study First Posted: 2018-03-29
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-07
• Last Update Posted: 2020-02-10
• Study Start: 2020-04
• Primary Completion: 2023-03
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

• Allogeneic hematopoietic stem cell transplantation from any donor other than full-matched related donor
• Age above 2 months and under 20 years
• Provide written informed consent from the parents (if <18) and child
• Free, informed and written consent, signed by the patient and investigator before any Study examination. If the patient is a minor by child (if possible) and both parents or child and the legal representative in case only one parent is alive

Exclusion Criteria

• Hematopoietic stem cell transplantation from full-matched related donor
• Females who are pregnant or currently nursing
• Any patient receiving cidofovir, ribavirin or any other anti-viral drug under development given in order to treat or prevent
• Current disease attributed to adenovirus infection
• Lack of affiliation to a social security scheme (as a beneficiary or assignee).Current disease attributed to adenovirus infection

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
rate of response to antiviral drugs	100 days	Success will be defined as undetectable level of DNA of Adv in blood after a maximum of 4 weeks of treatment. After 4 weeks of treatment any detectable level of Adv DNA will be considered as a failure.
rate of Adv blood infection according to levels of Adv DNA in stool samples.	100 days	Adv blood infection is defined as plasma Adv DNA level greater than 200 copies per milliliter

Secondary Outcome Measures

Name	Time	Method
Genotypic analysis of the Adv DNA polymerase	100 days
Incidence of Adv probable or proven disease	100 days
Detection and quantification of herpesviruses in blood	100 days
Incidence of acute digestive graft versus host disease (aGvHD)	100 days
Adv DNA levels > 5 log10 copies/ml in stool	100 days	measured at the end of treatment
Time required achieving 90% decrease of Adv load and undetectable Adv DNA.	100 days
Time required achieving 50% decrease of Adv load and undetectable Adv DNA.	100 days
Incidence of diarrhea	100 days
Overall survival.	100 days