Randomized trials of CMV prophylaxis in allogeneic HCT patients analyzed
| Study . | Year . | Methods . | Participant characteristics . | Study intervention . | SOC CMV management . | Outcomes measured . |
|---|---|---|---|---|---|---|
| 19 | 1981 | Randomized, double blind, placebo controlled, parallel groups | Transplantation type: allogeneic (16), autologous (3), syngeneic (1) | Patients randomized 1:1 to IV acyclovir 250 mg/m2 every 8 h or placebo from d −3 for total of 18 d | No additional management specified | HSV Infection, CMV infection |
| Age range: 6-51 y | ||||||
| Inclusion: HSV antibody titers ≥1:8 | ||||||
| 17 | 1983 | Randomized, double blind, placebo controlled, parallel groups | Transplantation type: matched RD or syngeneic | Patients randomized 1:1 to oral acyclovir 200 mg every 6 h or placebo from d −8 to d +35 | No additional management specified | HSV infection, CMV infection, effect of acyclovir on GVHD and survival |
| 18 | 1983 | Randomized, double blind, placebo controlled, parallel groups | Transplantation type: allogeneic matched or mismatched RD | Patients randomized 1:1 to IV acyclovir 5 mg/kg every 12 h or placebo during neutropenia (ANC <1 × 109/L) | No additional management specified | Incidence of HSV, incidence of CMV infection or disease, days of neutropenia |
| Serostatus: HSV R+ | ||||||
| 20 | 1986 | Randomized, double blind, placebo controlled, parallel groups, stratified by HSV serostatus | Transplantation type: allogeneic marrow transplantation | Patients randomized 1:1 to IV acyclovir 250 mg/m2 twice a day from d −5 to d +35, transitioned to oral acyclovir 400 mg every 8 h until d +180 | No additional management specified | Incidences of HSV infection, VZV infection, CMV infection |
| Age: ≥2 y | ||||||
| 25 | 1993 | Randomized, double blind, placebo controlled, parallel groups | Transplantation type: allogeneic marrow transplantation using total-body irradiation or busulfan-cyclophosphamide | Patients randomized 1:1 to IV ganciclovir 5 mg/kg twice daily or placebo beginning at engraftment for 5 d, then 5 mg/kg per day to d +100 | Upon positive viral cultures, patients removed from blinded study drug and treated with IV ganciclovir | Incidences of CMV infection, CMV disease, neutropenia |
| Age: ≥2 y | ||||||
| Serostatus: CMV R+ | ||||||
| 26 | 1993 | Randomized, double blind, parallel groups, placebo controlled | Transplantation type: allogeneic | Patients randomized 1:1 to IV ganciclovir 2.5mg/kg every 8 h from d −7 to d −1, then from engraftment (ANC ≥1 × 109/L) to d +120 6 mg/kg per day Mondays through Fridays, or placebo | Upon diagnosis of clinical CMV disease, patients removed from blinded study and treated with IV ganciclovir | CMV infection, CMV disease, study drug toxicity |
| Age: ≥12 y | Drug held for ANC <1 × 109/L, resumed at 6 mg/kg per d 3 times per wk | |||||
| Serostatus: CMV R+ | ||||||
| 21 | 1994 | Randomized, double blind, double dummy, 3 parallel groups | Transplantation type: HLA matched related or unrelated allogeneic | Patients randomized 1:1:1 to 1 of 3 arms | CMV disease or CMV infection treated at discretion of site investigator | Time to CMV infection, survival, time to CMV viremia |
| Age: ≥2 y | Arm A: IV acyclovir 500 mg/m2 every 8 h from d −5 to d +30, followed by oral acyclovir 800 mg every 6 h until 6 mo posttransplantation, adjusted to renal function | |||||
| Serostatus: CMV R+ or D+ | Arm B: IV acyclovir like arm A, placebo until 6 mo posttransplantation | |||||
| Arm C: 400 mg oral acyclovir every 6 h from d −5 to d +30, then placebo | ||||||
| 30 | 1996 | Randomized, double blind, parallel groups | Transplantation type: all allogeneic | Patients randomized 1:1 to IV ganciclovir 5 mg/kg twice daily or placebo beginning at engraftment for 5 d, then 5 mg/kg per day 6 d per wk to d +100 | If antigenemia or CMV viremia detected, study drug stopped, and IV ganciclovir administered | CMV disease, neutropenia |
| Age: all ages | Patients underwent CMV antigenemia testing and treated with IV ganciclovir with antigenemia of ≥3 cells per 2 slides | |||||
| Serostatus: CMV R+ | ||||||
| 23 | 2002 | Randomized, double blind, parallel groups | Transplantation type: allogeneic matched or mismatched, related or unrelated | All patients treated with IV acyclovir 500 mg/m2 every 8 h from d −5 to d +28, then randomized 1:1 into 2 arms | Preemptive therapy with IV ganciclovir or foscarnet based on laboratory evidence of infection, according to study site usual practice | Time to detection of CMV, time to death, time to CMV viremia, time to onset of CMV disease, time to other antiviral use, time to onset of CMV infection |
| Age: ≥13 y | Arm A: oral valacyclovir 2 g every 6 h until end of wk 22 posttransplantation | |||||
| Serostatus: CMV R+ or D+ | Arm B: oral acyclovir 800 mg every 6 h until end of wk 22 posttransplantation | |||||
| All doses adjusted to creatinine clearance | ||||||
| 24 | 2002 | Randomized trial, parallel groups | Transplantation type: allogeneic related or unrelated | All patients received IV ganciclovir 5 mg/kg twice daily from d −7 to −2, followed by IV acyclovir 10 mg/kg every 8 h from d −1 to engraftment; patients then randomized 1:1 into 2 arms | Upon detection of antigenemia, prophylaxis discontinued, and patients treated preemptively with administration of IV ganciclovir or foscarnet | Incidences of CMV antigenemia and CMV disease, adverse events |
| Age range: 1-55 y | Arm A: oral acyclovir 800 mg in adults, 18 mg/kg children, 5 times per day | |||||
| Serostatus: CMV R+ | Arm B: IV ganciclovir 5 mg/kg every weekday until d +100 | |||||
| All patients received IV immunoglobulin 500 mg/kg on days −6, 0, 7, 21, 35, 55, 76, 98 | ||||||
| 28 | 2003 | Randomized trial, parallel groups | Transplantation type: allogeneic related or unrelated | All patients received IV acyclovir 500 mg/m2 every 8 h from d 0 to engraftment (ANC ≥750 cells/µL for 2 d); patients then randomized 1:1 into 2 arms | Treatment of CMV infection or disease at discretion of site investigators | Incidences of CMV infection and CMV disease, incidence of neutropenia, survival |
| Age: ≥13 y | Arm A: oral valacyclovir 2 g every 6 h from engraftment to d +100 | |||||
| Serostatus: CMV R+ | ||||||
| Arm B: IV ganciclovir 5 mg/kg twice daily for 1 wk, then 6 mg/kg once daily 5 d per week | ||||||
| Doses reduced for patients with renal dysfunction | ||||||
| 27 | 2004 | Randomized trial, parallel groups | Transplantation type: allogeneic | IV ganciclovir 5 mg/kg twice daily from d −8 to d −1 for CMV R+ | No additional management specified; patients who stopped oral ganciclovir early treated with IV ganciclovir | Incidences of CMV infection, CMV disease |
| Serostatus: CMV R+ or D+ | Acyclovir 400 mg orally or 250 mg IV every 8 h for HSV R+ | |||||
| Randomized at engraftment 1:1 (ANC 500/µL and unsupported platelet recovery >20 × 109/L) | ||||||
| Arm A: IV ganciclovir 5 mg/kg 3 times weekly to d +84 | ||||||
| Arm B: oral ganciclovir 1 g every 8 h to d +84 | ||||||
| 22 | 2006 | Randomized, double blind, placebo controlled, stratified by presence of GVHD | Transplantation type: allogeneic | All patients seropositive to HSV given prophylactic acyclovir 250 mg/m2 every 12 h from d −7 to d +30 | CMV-specific management not mentioned | VZV disease at 1 y after transplantation, VZV infection after 1 y, HSV infection, CMV disease, toxicity, survival, VZV- and HSV-specific immune reconstitutions |
| Age: ≥10 y | Patients randomized 1:1 oral acyclovir 800 mg twice daily and started study drug between d 30 and d 100 and continued until 1 y after transplantation | |||||
| Inclusion: history of chicken pox | ||||||
| 29 | 2008 | Randomized, double blind, placebo controlled, stratified by transplantation type, sequential dose-escalation groups | Transplantation type: allogeneic | Randomized 3:1 to maribavir or placebo, dosing began at engraftment, d 14-30 after transplantation | Upon detection of CMV infection or diagnosis of CMV disease, study drug discontinued, and patients treated with anti-CMV antiviral at discretion of site investigators | Incidence and time of onset of CMV infection or CMV disease, incidence of CMV disease alone, use of preemptive antiviral therapy |
| Age: ≥18 y | Arm A: maribavir 100 mg twice daily | |||||
| Serostatus: CMV R+ | Arm B: maribavir 400 mg daily | |||||
| Arm C: maribavir 400 mg twice daily | ||||||
| Arm D: matching placebo twice daily, pooled from each dose level | ||||||
| 34 | 2011 | Randomized, double blind, placebo controlled, stratified by CMV serostatus and conditioning regimen, parallel groups | Transplantation type: allogeneic | Randomized 2:1 to maribavir or placebo 100 mg twice daily | Upon detection of CMV infection or diagnosis of CMV disease, study drug discontinued, and patients treated with anti-CMV antiviral at discretion of site investigators | Incidence of CMV disease through wk 24 after transplantation, time to onset of CMV disease, use of preemptive therapy, incidence of CMV infection, time to onset of CMV infection by antigenemia and PCR |
| Age: ≥18 y | Treatment had to start after engraftment and continue for up to 12 wk of treatment | |||||
| Serostatus: CMV D+ or R+ | ||||||
| 33 | 2013 | Randomized, double blind, placebo controlled, sequential dose-escalation groups | Transplantation type: allogeneic | Patients randomized 3:1 to brincidofovir (CMX001) or matching placebo; randomization and dosing initiated after engraftment, 14-30 d after transplantation | Preemptive therapy per study center standards | Failure to prevent progressive CMV infection: occurrence of CMV infection or increase in plasma CMV DNA level; rates of and reasons for discontinuation of study drug, use of preemptive therapy, trough levels of brincidofovir and cidofovir |
| Age: ≥18 y | Arm A: brincidofovir 40 mg weekly | |||||
| Serostatus: CMV R+ | Arm B: brincidofovir 100 mg weekly | |||||
| Arm C: brincidofovir 200 mg weekly | ||||||
| Arm D: brincidofovir 200 mg twice weekly | ||||||
| Arm E: brincidofovir 100 mg twice weekly | ||||||
| Arm F: matching placebo, pooled from each dose level | ||||||
| Treated for 9-11 wk depending on day of randomization after transplantation until wk 13 posttransplantation | ||||||
| 35 | 2014 | Randomized, double blind, placebo controlled, sequential dose-escalation groups | Transplantation type: allogeneic | Randomized 3:1 to letermovir or matching placebo; randomization and dosing began at engraftment between d 0 and d +40 after transplantation | Upon detection of active viral replication, study drug was discontinued and an alternative drug was initiated per study center standards | Incidence and time to onset of all-cause failure of prophylaxis against CMV infection; incidence and time of onset of CMV end-organ disease; detection of CMV replication; and discontinuation of study drug during the 12-wk period |
| Age: ≥18 y | Arm A: letermovir 60 mg daily | |||||
| Serostatus: CMV R+ | Arm B: letermovir 120 mg daily | |||||
| Arm C: letermovir 240 mg daily | ||||||
| Arm D: matching placebo daily | ||||||
| 32 | 2016 | Randomized, double blind, placebo controlled, stratified by CMV infection risk and center, parallel groups | Transplantation type: allogeneic | Randomized 2:1 to brincidofovir 100 mg twice weekly or matching placebo; treatment started between d 0 and d +28 independent of engraftment, continued until d +100 (wk 14 after transplantation) | Preemptive treatment per study center standards | Incidence of clinically significant CMV infection (defined as CMV disease or initiation of preemptive therapy) through wk 24 after transplantation; discontinuation for any reason or missing data on wk 24 considered event |
| Age: ≥18 y | Study requested CMV VL threshold of 1000 copies/mL to start preemptive therapy | |||||
| Serostatus: CMV R+ | ||||||
| 31 | 2017 | Randomized, double blind, placebo controlled, stratified by CMV risk and center, parallel groups | Type of transplantation: allogeneic | Randomized 2:1 to letermovir 480 mg per d (240 mg per d with concomitant cyclosporine use) or matching placebo | Preemptive treatment per study center standards | Incidence of clinically significant CMV infection (defined as CMV disease or initiation of preemptive therapy through wk 24 after transplantation); discontinuation for any reason or missing data on wk 24 considered event |
| Age: ≥18 y | Treatment started between d 0 and d +28 independent of engraftment, continued until d +100 (wk 14 after transplantation) | Study suggested CMV VL thresholds to initiate preemptive therapy: >150 copies/mL for high-risk patients, >300 copies/mL for low-risk patients | Proportion and time to clinically significant CMV infection through wk 14 posttransplantation; all-cause mortality through wk 24 | |||
| Serostatus: CMV R+ |
| Study . | Year . | Methods . | Participant characteristics . | Study intervention . | SOC CMV management . | Outcomes measured . |
|---|---|---|---|---|---|---|
| 19 | 1981 | Randomized, double blind, placebo controlled, parallel groups | Transplantation type: allogeneic (16), autologous (3), syngeneic (1) | Patients randomized 1:1 to IV acyclovir 250 mg/m2 every 8 h or placebo from d −3 for total of 18 d | No additional management specified | HSV Infection, CMV infection |
| Age range: 6-51 y | ||||||
| Inclusion: HSV antibody titers ≥1:8 | ||||||
| 17 | 1983 | Randomized, double blind, placebo controlled, parallel groups | Transplantation type: matched RD or syngeneic | Patients randomized 1:1 to oral acyclovir 200 mg every 6 h or placebo from d −8 to d +35 | No additional management specified | HSV infection, CMV infection, effect of acyclovir on GVHD and survival |
| 18 | 1983 | Randomized, double blind, placebo controlled, parallel groups | Transplantation type: allogeneic matched or mismatched RD | Patients randomized 1:1 to IV acyclovir 5 mg/kg every 12 h or placebo during neutropenia (ANC <1 × 109/L) | No additional management specified | Incidence of HSV, incidence of CMV infection or disease, days of neutropenia |
| Serostatus: HSV R+ | ||||||
| 20 | 1986 | Randomized, double blind, placebo controlled, parallel groups, stratified by HSV serostatus | Transplantation type: allogeneic marrow transplantation | Patients randomized 1:1 to IV acyclovir 250 mg/m2 twice a day from d −5 to d +35, transitioned to oral acyclovir 400 mg every 8 h until d +180 | No additional management specified | Incidences of HSV infection, VZV infection, CMV infection |
| Age: ≥2 y | ||||||
| 25 | 1993 | Randomized, double blind, placebo controlled, parallel groups | Transplantation type: allogeneic marrow transplantation using total-body irradiation or busulfan-cyclophosphamide | Patients randomized 1:1 to IV ganciclovir 5 mg/kg twice daily or placebo beginning at engraftment for 5 d, then 5 mg/kg per day to d +100 | Upon positive viral cultures, patients removed from blinded study drug and treated with IV ganciclovir | Incidences of CMV infection, CMV disease, neutropenia |
| Age: ≥2 y | ||||||
| Serostatus: CMV R+ | ||||||
| 26 | 1993 | Randomized, double blind, parallel groups, placebo controlled | Transplantation type: allogeneic | Patients randomized 1:1 to IV ganciclovir 2.5mg/kg every 8 h from d −7 to d −1, then from engraftment (ANC ≥1 × 109/L) to d +120 6 mg/kg per day Mondays through Fridays, or placebo | Upon diagnosis of clinical CMV disease, patients removed from blinded study and treated with IV ganciclovir | CMV infection, CMV disease, study drug toxicity |
| Age: ≥12 y | Drug held for ANC <1 × 109/L, resumed at 6 mg/kg per d 3 times per wk | |||||
| Serostatus: CMV R+ | ||||||
| 21 | 1994 | Randomized, double blind, double dummy, 3 parallel groups | Transplantation type: HLA matched related or unrelated allogeneic | Patients randomized 1:1:1 to 1 of 3 arms | CMV disease or CMV infection treated at discretion of site investigator | Time to CMV infection, survival, time to CMV viremia |
| Age: ≥2 y | Arm A: IV acyclovir 500 mg/m2 every 8 h from d −5 to d +30, followed by oral acyclovir 800 mg every 6 h until 6 mo posttransplantation, adjusted to renal function | |||||
| Serostatus: CMV R+ or D+ | Arm B: IV acyclovir like arm A, placebo until 6 mo posttransplantation | |||||
| Arm C: 400 mg oral acyclovir every 6 h from d −5 to d +30, then placebo | ||||||
| 30 | 1996 | Randomized, double blind, parallel groups | Transplantation type: all allogeneic | Patients randomized 1:1 to IV ganciclovir 5 mg/kg twice daily or placebo beginning at engraftment for 5 d, then 5 mg/kg per day 6 d per wk to d +100 | If antigenemia or CMV viremia detected, study drug stopped, and IV ganciclovir administered | CMV disease, neutropenia |
| Age: all ages | Patients underwent CMV antigenemia testing and treated with IV ganciclovir with antigenemia of ≥3 cells per 2 slides | |||||
| Serostatus: CMV R+ | ||||||
| 23 | 2002 | Randomized, double blind, parallel groups | Transplantation type: allogeneic matched or mismatched, related or unrelated | All patients treated with IV acyclovir 500 mg/m2 every 8 h from d −5 to d +28, then randomized 1:1 into 2 arms | Preemptive therapy with IV ganciclovir or foscarnet based on laboratory evidence of infection, according to study site usual practice | Time to detection of CMV, time to death, time to CMV viremia, time to onset of CMV disease, time to other antiviral use, time to onset of CMV infection |
| Age: ≥13 y | Arm A: oral valacyclovir 2 g every 6 h until end of wk 22 posttransplantation | |||||
| Serostatus: CMV R+ or D+ | Arm B: oral acyclovir 800 mg every 6 h until end of wk 22 posttransplantation | |||||
| All doses adjusted to creatinine clearance | ||||||
| 24 | 2002 | Randomized trial, parallel groups | Transplantation type: allogeneic related or unrelated | All patients received IV ganciclovir 5 mg/kg twice daily from d −7 to −2, followed by IV acyclovir 10 mg/kg every 8 h from d −1 to engraftment; patients then randomized 1:1 into 2 arms | Upon detection of antigenemia, prophylaxis discontinued, and patients treated preemptively with administration of IV ganciclovir or foscarnet | Incidences of CMV antigenemia and CMV disease, adverse events |
| Age range: 1-55 y | Arm A: oral acyclovir 800 mg in adults, 18 mg/kg children, 5 times per day | |||||
| Serostatus: CMV R+ | Arm B: IV ganciclovir 5 mg/kg every weekday until d +100 | |||||
| All patients received IV immunoglobulin 500 mg/kg on days −6, 0, 7, 21, 35, 55, 76, 98 | ||||||
| 28 | 2003 | Randomized trial, parallel groups | Transplantation type: allogeneic related or unrelated | All patients received IV acyclovir 500 mg/m2 every 8 h from d 0 to engraftment (ANC ≥750 cells/µL for 2 d); patients then randomized 1:1 into 2 arms | Treatment of CMV infection or disease at discretion of site investigators | Incidences of CMV infection and CMV disease, incidence of neutropenia, survival |
| Age: ≥13 y | Arm A: oral valacyclovir 2 g every 6 h from engraftment to d +100 | |||||
| Serostatus: CMV R+ | ||||||
| Arm B: IV ganciclovir 5 mg/kg twice daily for 1 wk, then 6 mg/kg once daily 5 d per week | ||||||
| Doses reduced for patients with renal dysfunction | ||||||
| 27 | 2004 | Randomized trial, parallel groups | Transplantation type: allogeneic | IV ganciclovir 5 mg/kg twice daily from d −8 to d −1 for CMV R+ | No additional management specified; patients who stopped oral ganciclovir early treated with IV ganciclovir | Incidences of CMV infection, CMV disease |
| Serostatus: CMV R+ or D+ | Acyclovir 400 mg orally or 250 mg IV every 8 h for HSV R+ | |||||
| Randomized at engraftment 1:1 (ANC 500/µL and unsupported platelet recovery >20 × 109/L) | ||||||
| Arm A: IV ganciclovir 5 mg/kg 3 times weekly to d +84 | ||||||
| Arm B: oral ganciclovir 1 g every 8 h to d +84 | ||||||
| 22 | 2006 | Randomized, double blind, placebo controlled, stratified by presence of GVHD | Transplantation type: allogeneic | All patients seropositive to HSV given prophylactic acyclovir 250 mg/m2 every 12 h from d −7 to d +30 | CMV-specific management not mentioned | VZV disease at 1 y after transplantation, VZV infection after 1 y, HSV infection, CMV disease, toxicity, survival, VZV- and HSV-specific immune reconstitutions |
| Age: ≥10 y | Patients randomized 1:1 oral acyclovir 800 mg twice daily and started study drug between d 30 and d 100 and continued until 1 y after transplantation | |||||
| Inclusion: history of chicken pox | ||||||
| 29 | 2008 | Randomized, double blind, placebo controlled, stratified by transplantation type, sequential dose-escalation groups | Transplantation type: allogeneic | Randomized 3:1 to maribavir or placebo, dosing began at engraftment, d 14-30 after transplantation | Upon detection of CMV infection or diagnosis of CMV disease, study drug discontinued, and patients treated with anti-CMV antiviral at discretion of site investigators | Incidence and time of onset of CMV infection or CMV disease, incidence of CMV disease alone, use of preemptive antiviral therapy |
| Age: ≥18 y | Arm A: maribavir 100 mg twice daily | |||||
| Serostatus: CMV R+ | Arm B: maribavir 400 mg daily | |||||
| Arm C: maribavir 400 mg twice daily | ||||||
| Arm D: matching placebo twice daily, pooled from each dose level | ||||||
| 34 | 2011 | Randomized, double blind, placebo controlled, stratified by CMV serostatus and conditioning regimen, parallel groups | Transplantation type: allogeneic | Randomized 2:1 to maribavir or placebo 100 mg twice daily | Upon detection of CMV infection or diagnosis of CMV disease, study drug discontinued, and patients treated with anti-CMV antiviral at discretion of site investigators | Incidence of CMV disease through wk 24 after transplantation, time to onset of CMV disease, use of preemptive therapy, incidence of CMV infection, time to onset of CMV infection by antigenemia and PCR |
| Age: ≥18 y | Treatment had to start after engraftment and continue for up to 12 wk of treatment | |||||
| Serostatus: CMV D+ or R+ | ||||||
| 33 | 2013 | Randomized, double blind, placebo controlled, sequential dose-escalation groups | Transplantation type: allogeneic | Patients randomized 3:1 to brincidofovir (CMX001) or matching placebo; randomization and dosing initiated after engraftment, 14-30 d after transplantation | Preemptive therapy per study center standards | Failure to prevent progressive CMV infection: occurrence of CMV infection or increase in plasma CMV DNA level; rates of and reasons for discontinuation of study drug, use of preemptive therapy, trough levels of brincidofovir and cidofovir |
| Age: ≥18 y | Arm A: brincidofovir 40 mg weekly | |||||
| Serostatus: CMV R+ | Arm B: brincidofovir 100 mg weekly | |||||
| Arm C: brincidofovir 200 mg weekly | ||||||
| Arm D: brincidofovir 200 mg twice weekly | ||||||
| Arm E: brincidofovir 100 mg twice weekly | ||||||
| Arm F: matching placebo, pooled from each dose level | ||||||
| Treated for 9-11 wk depending on day of randomization after transplantation until wk 13 posttransplantation | ||||||
| 35 | 2014 | Randomized, double blind, placebo controlled, sequential dose-escalation groups | Transplantation type: allogeneic | Randomized 3:1 to letermovir or matching placebo; randomization and dosing began at engraftment between d 0 and d +40 after transplantation | Upon detection of active viral replication, study drug was discontinued and an alternative drug was initiated per study center standards | Incidence and time to onset of all-cause failure of prophylaxis against CMV infection; incidence and time of onset of CMV end-organ disease; detection of CMV replication; and discontinuation of study drug during the 12-wk period |
| Age: ≥18 y | Arm A: letermovir 60 mg daily | |||||
| Serostatus: CMV R+ | Arm B: letermovir 120 mg daily | |||||
| Arm C: letermovir 240 mg daily | ||||||
| Arm D: matching placebo daily | ||||||
| 32 | 2016 | Randomized, double blind, placebo controlled, stratified by CMV infection risk and center, parallel groups | Transplantation type: allogeneic | Randomized 2:1 to brincidofovir 100 mg twice weekly or matching placebo; treatment started between d 0 and d +28 independent of engraftment, continued until d +100 (wk 14 after transplantation) | Preemptive treatment per study center standards | Incidence of clinically significant CMV infection (defined as CMV disease or initiation of preemptive therapy) through wk 24 after transplantation; discontinuation for any reason or missing data on wk 24 considered event |
| Age: ≥18 y | Study requested CMV VL threshold of 1000 copies/mL to start preemptive therapy | |||||
| Serostatus: CMV R+ | ||||||
| 31 | 2017 | Randomized, double blind, placebo controlled, stratified by CMV risk and center, parallel groups | Type of transplantation: allogeneic | Randomized 2:1 to letermovir 480 mg per d (240 mg per d with concomitant cyclosporine use) or matching placebo | Preemptive treatment per study center standards | Incidence of clinically significant CMV infection (defined as CMV disease or initiation of preemptive therapy through wk 24 after transplantation); discontinuation for any reason or missing data on wk 24 considered event |
| Age: ≥18 y | Treatment started between d 0 and d +28 independent of engraftment, continued until d +100 (wk 14 after transplantation) | Study suggested CMV VL thresholds to initiate preemptive therapy: >150 copies/mL for high-risk patients, >300 copies/mL for low-risk patients | Proportion and time to clinically significant CMV infection through wk 14 posttransplantation; all-cause mortality through wk 24 | |||
| Serostatus: CMV R+ |
ANC, absolute neutrophil count; D, donor; GVHD, graft-versus-host disease; HSV, herpes simplex virus; PCR, polymerase chain reaction; R, recipient; RD, related donor; SOC, standard of care; VZV, varicella zoster virus.