Clinical trial NCT03481244: Treatment of Adenovirus Disseminated Infections in Hematopoietic Stem Cell Transplant Patients With Adenovirus Digestive Replication
Official title: Treatment of Adenovirus Disseminated Infections in Hematopoietic Stem Cell Transplant Patients With Adenovirus Digestive Replication- A Pharmaco-epidemiological Prospective Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Patients Who Underwent Allograft
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2018-03-29
Enrollment: 400
Sex: ALL
Minimum age (years): 2
Maximum age (years): 20
Standard ages: CHILD
ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: any patient age above 2 month- and under 20 year- old receiving an allogeneic hematopoietic stem cell transplant

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.


Eligibility criteria: 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

Primary outcomes:
measure: rate of Adv blood infection according to levels of Adv DNA in stool samples.
timeFrame: 100 days
measure: rate of response to antiviral drugs
timeFrame: 100 days
Secondary outcomes:
measure: Adv DNA levels > 5 log10 copies/ml in stool
timeFrame: 100 days
measure: Time required achieving 50% decrease of Adv load and undetectable Adv DNA.
timeFrame: 100 days
measure: Time required achieving 90% decrease of Adv load and undetectable Adv DNA.
timeFrame: 100 days
measure: Incidence of Adv probable or proven disease
timeFrame: 100 days
measure: Incidence of diarrhea
timeFrame: 100 days
measure: Incidence of acute digestive graft versus host disease (aGvHD)
timeFrame: 100 days
measure: Overall survival.
timeFrame: 100 days
measure: Incidence of Adv probable or proven disease
timeFrame: 100 days
measure: Genotypic analysis of the Adv DNA polymerase
timeFrame: 100 days
measure: Detection and quantification of herpesviruses in blood
timeFrame: 100 days
Other outcomes:
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