ORPHAVIC: A French Cohort of Transplant Recipients With CMV Infection : Risk Factors for Antiviral Resistance in the Prophylaxis Era.

Sponsor

University Hospital, Limoges (Other)

Overall Status

Completed

CT.gov ID

NCT02067169

Collaborator

(none)

408

Enrollment

Locations

Duration (Months)

10.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Resistance to antivirals is a growing problem in transplantation.that may concerns up to 5% of patients treated for cytomegalovirus (CMV) syndrome or disease in recent per-protocol studies. This prevalence vary with the organ transplanted and the degree of viral replication and immunosuppression. Less data are available to date from real-life cohorts of patients, and there is no systematic survey of resistance in Europe or in the US. Non response to treatment concerns a larger group of patients and can result either from emergence of a resistant strain (virological resistance), from inadequate dosage of antivirals, or a high degree of immunosuppression, with a poor CMV immune response. The respective clinical impact of virological resistance and clinical resistance (of pharmacological or immunological origin) on graft outcome and long-term survival of patients has never been assessed. High viral loads and persistent replication associated to prolonged exposure to antivirals are known to favor the emergence of resistant strains. Though epidemiology of resistant strains, role of multiple infections, impact of various mutations on degree of resistance to antivirals and outcome remains to be further studied. Most studies are per-protocol studies or short-term studies conducted on limited populations. There are no data in real-life of transplanted patients at the era of enlarged prophylaxis except those from the French survey for cytomegalovirus resistance cohort opened at the end of 2006. From the first data collected on 346 patients we shown a 10,6% prevalence of non-response to therapy with 5,2% of virological resistance (6,1% incidence at one year on 214 patients) with a trend to poorer outcome in case of virological resistance and to the absence of impact of prophylaxis versus preemptive therapy, though larger populations and prolonged follow-up are requested to fulfill all objectives.

We therefore aim to constitute a prolonged survey cohort for CMV resistance with a large number of patients and a prolonged follow-up, to gather data on resistance to antivirals in real-life of transplant patients in an organized data bank, This cohort is in the continuum of our previous cohort started in 2006, granted by the Hospital Clinical Research Program Interregional (PHRC), with the same major objectives and prolonged follow-up of patients.

Condition or Disease	Intervention/Treatment	Phase
Transplant Recipients With CMV Infection	Biological: CMV Infection

Study Design

Study Type:

Observational

Actual Enrollment :

408 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A French Cohort of Transplant Recipients With CMV Infection : Risk Factors for Antiviral Resistance in the Prophylaxis Era. Survey of Pharmacological and Virological Resistance of Cytomegalovirus to Antiviral Therapy in Transplantation.

Study Start Date :

Jan 1, 2012

Actual Primary Completion Date :

May 1, 2016

Actual Study Completion Date :

May 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
CMV infection allograft recipient with active CMV infection	Biological: CMV Infection Routine follow-up (viral load, creatininaemia, neutrophil count, isolation of CMV strains when possible) and biological sample collection for . Resistance testing towards any antiviral available by genotype and phenotype (when an isolate is obtained) when resistance criteria are fulfilled. Plasma collection at treatment initiation, and in case of neutropenia, for antiviral dosage.

Arm

Intervention/Treatment

CMV infection

allograft recipient with active CMV infection

Biological: CMV Infection

Routine follow-up (viral load, creatininaemia, neutrophil count, isolation of CMV strains when possible) and biological sample collection for . Resistance testing towards any antiviral available by genotype and phenotype (when an isolate is obtained) when resistance criteria are fulfilled. Plasma collection at treatment initiation, and in case of neutropenia, for antiviral dosage.

Outcome Measures

Primary Outcome Measures

prevalence and incidence of resistance of cytomegalovirus [3 weeks]
Non response to therapy is defined as persistent viral replication after more than 3 weeks of appropriate antiviral treatment, with or without clinical manifestations.

Secondary Outcome Measures

pharmacological and virological resistance [2 years]
Measure the respective incidence of pharmacological and virological resistance

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

allograft recipient with active CMV infection,
or patient from the previous cohort, without opposition to biological collection of samples

Exclusion Criteria:

not willing to participate, no health insurance

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Virologie	Amiens	France	80
2	Virologie	Angers	France	49
3	Virologie	Besancon	France	25
4	Virologie - Hôpital Avicenne	Bobigny	France	93
5	Virologie	Bordeaux	France	33
6	Virologie	Brest	France	29
7	Virologie	Caen	France	14
8	Virologie	Clermont Ferrand	France	63
9	AP-HP - Hôpital Beaujon - Virologie	Clichy	France	92118
10	AP-HP - Hôpital MONDOR - Virologie	Creteil	France	94010
11	Virologie	Dijon	France	21
12	Virologie	Grenoble	France	38
13	Centre Chirurgical Marie Lannelongue	Le Plessis Robinson	France	92350
14	Virologie	Lille	France	59
15	Bactériologie Virologie	Limoges	France	87042
16	HCLYON - Virologie - Hôpital La Croix Rousse	Lyon	France	69314
17	Virologie	Lyon	France	69
18	Virologie - AP-HM - La Timone	Marseille	France	13385
19	Virologie	Montpellier	France	34
20	Virologie	Nancy	France	54
21	Virologie	Nantes	France	44
22	Virologie	Nimes	France	30
23	AP-HP - Hôpital Saint-Antoine - Virologie	Paris	France	75571
24	AP-HP - Hôpital Georges Pompidou - Virologie	Paris	France	75908
25	AP-HP - Hôpital TENON - Virologie	Paris	France	75970
26	Virologie - Hôpital BICHAT	Paris	France	75
27	Virologie - Hôpital La Pitié Salpétrière	Paris	France	75
28	Virologie - Hôpital NECKER	Paris	France	75
29	Virologie - Hôpital SAINT-LOUIS	Paris	France	75
30	Virologie	Poitiers	France	86
31	Virologie	Reims	France	51
32	Virologie	Rennes	France	35
33	Virologie	Rouen	France	76
34	Virologie	Saint-etienne	France	42
35	Virologie	Strasbourg	France	67
36	Virologie	Toulouse	France	31
37	Virologie	Tours	France	37
38	Virologie - Hôpital Paul Brousse	Villejuif	France	94