Clinical trial NCT02973464: The Strategy in the Prevention of Renal Post-transplant Cytomegalovirus Infection Among Chinese Population
Official title: The Strategy in the Prevention of Renal Post-transplant Cytomegalovirus Infection Among Chinese Population
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Renal Transplant Recipients
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
First posted: 2016-11-25
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Renal Transplant Recipients

Brief summary: This study evaluates the safety and availability of oral valganciclovir(VGC) at the does of 450mg daily begin within 10 days after renal transplantation, and till to Day 100 posttransplant. Compare to the guidelines for effective antiviral prophylaxis, the investigators divide these patients into three groups in random. One third will oral VGC 450mg daily as mentioned above; one third will oral VGC 900mg daily; and the other one third will intravenous GCV 5mg/kg daily within the first 14 days posttransplant, and continue to oral GCV 1g 3 times daily till to Day 100 posttransplant; with does adjusted per renal function for all agents.

Detailed description: Human Cytomegalovirus(CMV), a kind of β-hepersvirus, which is a common opportunistic pathogen. The ubiquity of CMV infection in human beings had been verified; and the CMV-IgG seropositive rate is 97% among healthy population, most of them are at the state of latent infection. When immunosuppressed, such as for renal transplant recipients, the incidence of CMV infection and disease increase obviously. The posttransplant CMV infection would induce allgraft rejection, impact on allgraft and recipients survival, as well as contribute to the serious complications.Many studies show that giving effective antivirus drugs after transplantation is benifit to recipients.

Nowadays,the strategy of intravenous GCV GCV 5mg/kg daily or oral GCV 1g 3 times daily, which is the recommended treatment for CMV disease posttransplantation.Resent date show that VGC is an oral prodrug of GCV. When VGC is absorbed in the intestinal wall and liver, it is rapidly metabolized to ganciclovir. As a contemporary study, IV GCV 5mg/kg/day will approach to a similar area under the curve to VGC 900mg daily. The bioavailability of ganciglovir from valganciclovir is 10 times of GCV by oral. For recipients, oral therapy is more safety and convinient, so that it will reduce frequent hospitalizations. As many researches, it is indicated that oral VGC 450mg daily can also reduce the adverse events resulting from posttransplant CMV infection, there is no significantly statistic differences when compared with oral VGC 900mg daily. Simultaneously, lower dose could decrease the risk of leukopenia and ease the burden for recipients.

This study is a single-center, prospective, observational, corhort study. According to the inclusion and exclusion criteria, the investigators will recruit 450 patients. And every one will be followed up for at least 12 months unless death or graft loss, the specific duration is at baseline, weekly within the first 3 months posttransplantation, month 4, month 5, month 6, month 9, and month 12. Recipients will be followed for CMV-DNA, CMV-pp65, CMV antigenemia, blood routine test, urinalysis, liver function, renal fuction and the chest X-ray films. Inverstigators should collect the date of recipient as below: general conditions, such as age, sex, weight and so on; primary reason for transplant; donor/recipient CMV serostatus; biopsy-prove acute rejection; opportunistic infections; NODAT; etc. And Chi-square or Fisher's exact test will be used as appropriate to compare categorical variables, and it is considered as statistically significant when the 2-sided P-value\<0.05. Definitively, conclusion will be come out to verify the safety and availability of our protocol.

Eligibility criteria: Inclusion Criteria:

* 1.65 years old\>=Age\>=18 years old, male or female
* 2.Renal transplantation first time
* 3.CMV serology donor-positive(D+) or recipient-positive(R+) renal transplant recipients

Exclusion Criteria:

* 1.Those who are allergic or resistant to Acyclovir, Valaciclovir, Ganciclovir, Valganciclovir
* 2.HIV, hepatitis B or hepatitis C patients
* 3.Not in pregnancy or lactation, pregnancy test was negative, and promise not to be pregnancy during treatment
* 4.Male with a pregnant partner; or lactation
* 5.Suspected CMV disease at enrolment
* 6.Use of anti-CMV therapy within 30 days prior to study
* 7.Multiple organ transplantation
* 8.Uncontrolled diarrhea or evidence of malabsorption
* 9.Liver function tests\>3 times the upper level of normal

Primary outcomes:
measure: incidence of CMV infection and disease
timeFrame: within the first 1 year after renal transplant
Secondary outcomes:
measure: incidence of CMV infection and disease
timeFrame: within the first 3 and 6 months after renal transplant respectively
measure: GCV-resistant CMV infection
timeFrame: within the first 1 year after renal transplant
measure: mean estimated renal function, allograft survival and patient survival
timeFrame: within the first 1 year after renal transplant
measure: incidence of acute rejection
timeFrame: within the first 1 year after renal transplant
measure: other opportunistic infections
timeFrame: within the first 1 year after renal transplant
measure: adverse events, such as NODAT
timeFrame: within the first 1 year after renal transplant
Other outcomes:
Locations:
city: Xi'an
country: China
facility: the First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
Study officials:
affiliation: First Affiliated Hospital Xi'an Jiaotong University
name: Xiaoming D Ding, PhD
role: PRINCIPAL_INVESTIGATOR
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