Kidney Transplant
Conditions
Keywords
Kidney Transplant, cytomegalovirus, letemovir, valganciclovir, Randomized control
Brief summary
the existing anti-CMV drugs mainly include valganciclovir, ganciclovir and foscarnet sodium, all of which act on DNA polymerase (pUL54), making them prone to cross resistance. DNA synthesis in normal cell is also catalyzed by DNA polymerase, which can also inhibit normal cell production, especially in metabolically active bone marrow cells, leading to bone marrow suppression. In addition, these drugs are mainly metabolized by the kidneys, causing damage to proximal renal tubular cells. Therefore, it is necessary to closely monitor the patient's renal function and adjust the dosage. Overall, the medical demand for effective and well-tolerated treatment methods for CMV infection management in kidney transplant recipients remains unmet, and safer anti-CMV drugs are urgently needed. The target of letemovir is the CMV DNA terminal enzyme complex, which is different from the target of existing anti-CMV drugs, and does not exhibit cross resistance. Moreover, this target does not have a corresponding substance in mammalian cells and does not exhibit toxicity similar to DNA polymerase targets. In addition, letemovir is mainly metabolized by the liver, and urinary excretion can be ignored (\<2% dose), so there is no need to adjust the dose according to renal function. Phase III registered clinical studies abroad have shown that letemovir is not inferior to valganciclovir in preventing CMV disease in kidney transplant recipients. Additionally, letemovir is safer and has a lower incidence of adverse reactions, especially leukopenia or granulocytopenia. However, there is still a lack of data on the use of kidney transplantation in Chinese population. The aim of this study was to evaluate the efficacy and safety of letamovir in preventing CMV infection and CMV disease in kidney transplant recipients in China.
Detailed description
the existing anti-CMV drugs mainly include valganciclovir, ganciclovir and foscarnet sodium, all of which act on DNA polymerase (pUL54), making them prone to cross resistance. DNA synthesis in normal cell is also catalyzed by DNA polymerase, which can also inhibit normal cell production, especially in metabolically active bone marrow cells, leading to bone marrow suppression. In addition, these drugs are mainly metabolized by the kidneys, causing damage to proximal renal tubular cells. Therefore, it is necessary to closely monitor the patient's renal function and adjust the dosage. Overall, the medical demand for effective and well-tolerated treatment methods for CMV infection management in kidney transplant recipients remains unmet, and safer anti-CMV drugs are urgently needed. The target of letemovir is the CMV DNA terminal enzyme complex, which is different from the target of existing anti-CMV drugs, and does not exhibit cross resistance. Moreover, this target does not have a corresponding substance in mammalian cells and does not exhibit toxicity similar to DNA polymerase targets. In addition, letemovir is mainly metabolized by the liver, and urinary excretion can be ignored (\<2% dose), so there is no need to adjust the dose according to renal function. Phase III registered clinical studies abroad have shown that letemovir is not inferior to valganciclovir in preventing CMV disease in kidney transplant recipients. Additionally, letemovir is safer and has a lower incidence of adverse reactions, especially leukopenia or granulocytopenia. However, there is still a lack of data on the use of kidney transplantation in Chinese population. The aim of this study was to evaluate the efficacy and safety of letamovir in preventing CMV infection and CMV disease in kidney transplant recipients in China.
Interventions
DRUGLetermovir
Drug name: Letermovir.
DRUGValganciclovir
Valganciclovir.
Sponsors
Chinese People's Liberation Army Northern Theater Command General Hospital
The First Hospital of Jilin University
The Affiliated Hospital of Qingdao University
Qianfo Mountain Hospital, Shandong Province
The First Affiliated Hospital of Anhui Medical University
Eastern Theater General Hospital
Shu lan Hospital
Shanghai Zhongshan Hospital
Tongji Hospital
The Second Xiangya Hospital, Central South University
The First Affiliated Hospital of Zhengzhou University
Second Affiliated Hospital of Guangzhou Medical University
First Affiliated Hospital, Sun Yat-Sen University
Beijing Chao Yang Hospital
RenJi Hospital
Nanfang Hospital, Southern Medical University
Tsinghua Changgeng Hospital, Beijing
First Affiliated Hospital Xi'an Jiaotong University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- 1) Age ≥18 years old, gender unlimited. 2) Receiving the first kidney transplant. 3) Be within 0 (ie, day of transplantation) to 7 days (inclusive) post-kidney transplant at the time of randomization. 4\) Obtain informed consent signed .
Exclusion criteria
* 1)Received a previous solid organ transplant or HSCT. 2)Is a multi-organ transplant recipient (eg, kidney-pancreas). Note: Double kidney transplant recipients (ie, transplant of two kidneys from the same donor to the same recipient simultaneously) will be excluded. 3)Has a history of CMV disease or suspected CMV disease within 6 months prior to randomization. 4)Has evidence of CMV viremia at any time from the signing of the ICF or the transplant procedure until the randomization period; 5)Has suspected or known hypersensitivity to active or inactive ingredients of LET formulations, VGCV, GCV, formulations. 6)Is on dialysis or plasmapheresis at the time of randomization. Note: For the purposes of this protocol, dialysis includes hemofiltration. Participant who: (1) has had dialysis or plasmapheresis within 7 days (inclusive) post-transplant but is not on dialysis or plasmapheresis at the time of randomization; and (2) is expected to remain off dialysis or plasmapheresis may be enrolled, provided that all other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of CMV disease at 52 weeks after transplantation | 52 weeks after transplantation | Proportion of subjects diagnosed with CMV disease at week 52 after transplantation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of CMV disease at 14/24 weeks after transplantation | 14/24 weeks after transplantion | Proportion of subjects diagnosed with CMV disease at week 14/26 after transplantation. |
| Time of CMV onset 52 weeks after transplantation | 52 weeks after transplantation | From the day of transplant to the first diagnosis of CMV disease. |
| Incidence of CMV DNaemia at 14/26/52 weeks after transplantation | 14/24/52 weeks after transplantion | Proportion of subjects diagnosed with CMV DNaemia at week 14/26/52 after transplantation. |
| Incidence and severity of all adverse events | 52 weeks after transplantation | Proportion of subjects with any AE that occurred from the time the study intervention was assigned to 14 days after the study intervention was terminated. Saes will only be reported 14 days after stopping the study intervention until week 52 after transplantation. |
Countries
China
Contacts
Primary ContactXiaoming Ding
Backup ContactYihan Wang
Outcome results
None listed