CompletedNCT00227370ValganUpdated Oct 4, 2024Results posted

Comparison of Oral Valganciclovir and Placebo for the Prevention of Cytomegalovirus (CMV) After Lung Transplantation

A Phase 3 interventional study of valganciclovir and Placebo in Cytomegalovirus Infections, sponsored by Duke University. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-10-04.

Sponsored by Duke University · Phase 3, Interventional, and Prevention

Phase: Phase 3
Study type: Interventional
Enrollment: 136
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

The study evaluated the efficacy and safety of a prolonged, continuous course of Valganciclovir (Valgan) in the prevention of CMV by comparing 3 months of Vaglanciclovir, the standard of care upon initiation of the study, to 12 months of Valganciclovir.

Read the detailed description

A multi-center two phase, double-blind, placebo controlled, randomized prospective study of 130 lung transplant recipients. Patients will be screened and consented prior to transplant. All consented patients will receive IV ganciclovir within 24 hours of transplant for not more than 14 days. Patients will enroll in Phase I of the study is an open label safety and efficacy analysis of three months of oral valganciclovir in adult transplant recipients who are at risk for CMV. After completion of 3 months of open label therapy, patients that meet the criteria for Phase II of the study will be randomized to 9 months of blinded therapy (Placebo/Valgan). Phase II of the study is designed to assess the efficacy of short course sequential IV ganciclovir followed by oral valganciclovir as compared to the extended period of oral valganciclovir prophylaxis in the prevention of CMV disease in at risk lung transplant recipients

Conditions studied

Cytomegalovirus Infections

Browse trials for

Cytomegalovirus Infections 359

Keywords

Acute rejection
Non-CMV infections
Resistance

In context

Cytomegalovirus Infections

359 studies on the registry are indexed under Cytomegalovirus Infections; 59 are open to participants now.

This study's enrollment of 136 is above the median of 60 across 233 interventional studies indexed under Cytomegalovirus Infections.

Browse Cytomegalovirus Infections studies →

Lead sponsor

Duke University is the lead sponsor of 2,025 studies on the registry; 275 are open to participants now.

Of its 194 completed or terminated interventional studies of FDA-regulated products, 159 (82%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Inclusion Criteria for Phase I:

Adult lung transplant recipients age 18 or older
At risk for CMV (donor or recipient serology must be positive for CMV)
Adequate hematological and renal function,
On intravenous (IV) ganciclovir within 24 hours of surgery
Agreement to use effective methods of contraception
Negative pregnancy
Tolerate oral medications within 2 weeks of transplant
Negative baseline CMV PCR
Able to understand and sign the informed consent

Exclusion Criteria for Phase 1:

Repeat transplantation
Mechanical ventilation at study entry
Oral or intravenous ganciclovir treatment outside the study protocol
Invasive fungal infection
Participation in another investigational study
Acute CMV infection or disease
Anti-CMV therapy within 30 days before enrollment
Uncontrolled diarrhea or malabsorption
Allergic reaction to study drug
Required use of prohibited medications
Lactating women
Pregnancy
Renal failure

Inclusion Criteria for Phase II:

Negative serial post transplant PCRs at day 75
Negative bronchial cultures for CMV
Adequate hematological and renal function at day 75
IV ganciclovir for up to 2 weeks post operation and open label up to day 90
Effective contraceptives
Negative pregnancy

Exclusion Criteria Phase II:

Renal failure
Serious adverse events (SAE) related to study drug
CMV disease (study endpoint)
Withdraw consent for Phase II

Study design

Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Care provider, Investigator)
Enrollment: 136 participants (actual)

Study arms

Active comparator
1
Valganciclovir 900 mg QD for 9 months post lung transplant.
Drug: valganciclovir
Placebo comparator
2
placebo for 9 months post lung transplant
Other: Placebo

Interventions

Drugvalganciclovir
valgan 900mg QD x 9 months post lung transplant
Also known as: valcyte
OtherPlacebo

What researchers measure

Primary outcomes

Incidence of CMV End Organ Disease
The primary study end point was CMV end-organ disease determined by positive tissue immunostain or characteristic histopathology assessed for within 300 days post randomization.
Time frame: over the course of 300 days after randomization
Incidence of CMV Syndrome
CMV clinical syndrome, with either positive serum PCR or positive culture for CMV from bronchoalveolar lavage and at least 2 of the following: fever, leukopenia, thrombocytopenia, elevated liver function test results malaise, reduction in pulmonary function (FEV1) greater than 20percent of baseline, or radiographic infiltrate consistent with CMV (all in the absence of other causes)
Time frame: over the course of 300 days after randomization

Secondary outcomes

Any CMV Infection
Inclusive of CMV syndrome, disease, or infection not meeting primary end point.
Time frame: over the course of 300 days post randomization
Biopsy Proven Acute Lung Rejection
Time frame: over the course of 300 days of randomization
Non-CMV Infection
non cmv opportunistic infections
Time frame: over the course of 300 days after randomization
Severity of Viremia
upon diagnosis of cmv disease, the number of CMV DNA copies/mL as measured by PCR
Time frame: over the course of 300 days after randomization
Ganciclovir Resistance
UL97 genotyping was done on all positive samples for CMV DNA at 1000 copies/mL, with resistance defined by the presence of 1 or more mutations shown by marker transfer to confer phenotypic ganciclovir resistance
Time frame: over the course of 300 days post randomization

Results

Posted Apr 29, 2013

Participant flow

Prospective subjects were screened and enrolled from July 2003 - January 2007 at 11 US lung transplant centers. 189 subjects were screened and 157 met inclusion criteria and were therefore enrolled in the study.

Participant flow — Overall Study
Milestone	Placebo Group	Treatment Group
Started	66	70
Completed	45	46
Not completed	21	24
Withdrew: Withdrawal by subject	1	2
Withdrew: Death	3	4
Withdrew: Adverse event	6	11
Withdrew: Physician decision	9	6
Withdrew: Other reasons	2	1

Outcome measures

PrimaryIncidence of CMV End Organ Disease

The primary study end point was CMV end-organ disease determined by positive tissue immunostain or characteristic histopathology assessed for within 300 days post randomization.

Time frame:: over the course of 300 days after randomization
Reported as:: Number · participants

Incidence of CMV End Organ Disease
participants	Placebo Group	Treatment Group
Incidence of CMV End Organ Disease	21	1

PrimaryIncidence of CMV Syndrome

CMV clinical syndrome, with either positive serum PCR or positive culture for CMV from bronchoalveolar lavage and at least 2 of the following: fever, leukopenia, thrombocytopenia, elevated liver function test results malaise, reduction in pulmonary function (FEV1) greater than 20percent of baseline, or radiographic infiltrate consistent with CMV (all in the absence of other causes)

Time frame:: over the course of 300 days after randomization
Reported as:: Number · participants

Incidence of CMV Syndrome
participants	Placebo Group	Treatment Group
Incidence of CMV Syndrome	13	0

SecondaryAny CMV Infection

Inclusive of CMV syndrome, disease, or infection not meeting primary end point.

Time frame:: over the course of 300 days post randomization
Reported as:: Number · participants

Any CMV Infection
participants	Placebo Group	Treatment Group
Any CMV Infection	42	7

SecondaryBiopsy Proven Acute Lung Rejection

Time frame:: over the course of 300 days of randomization
Reported as:: Number · participants

Biopsy Proven Acute Lung Rejection
participants	Placebo Group	Treatment Group
Biopsy Proven Acute Lung Rejection	22	15

SecondaryNon-CMV Infection

non cmv opportunistic infections

Time frame:: over the course of 300 days after randomization
Reported as:: Number · participants

Non-CMV Infection
participants	Placebo Group	Treatment Group
Non-CMV Infection	35	38

SecondarySeverity of Viremia

upon diagnosis of cmv disease, the number of CMV DNA copies/mL as measured by PCR

Time frame:: over the course of 300 days after randomization
Reported as:: Median · CMV copies/mL

Severity of Viremia
CMV copies/mL	Placebo Group	Treatment Group
Severity of Viremia	110,000 (40,000 to 361,569)	3,200 (2,700 to 3,700)

SecondaryGanciclovir Resistance

UL97 genotyping was done on all positive samples for CMV DNA at 1000 copies/mL, with resistance defined by the presence of 1 or more mutations shown by marker transfer to confer phenotypic ganciclovir resistance

Time frame:: over the course of 300 days post randomization
Reported as:: Number · participants

Ganciclovir Resistance
participants	Placebo Group	Treatment Group
Ganciclovir Resistance	1	2

Adverse events

Collected over Adverse events were collected from the first day posttransplant to the close of the study (day 390); however they were stratified by Phases (I and II) therefore SAEs are only reported for phase II subjects (ie only randomized subjects).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Placebo Group	—	35/66 (53%)	64/66 (97%)
Treatment Group	—	38/70 (54.3%)	70/70 (100%)

Most frequent serious events

Showing 10 of 33

Most frequent serious events
Event	Placebo Group	Treatment Group
Opportunistic Infections, all organ systemsInfections and infestations	31/66	32/70
Opportunistic Infections, all organ systems, moderateInfections and infestations	17/66	17/70
Opportunistic Infections, all organ systems, mildInfections and infestations	11/66	8/70
NEUTROPENIAImmune system disorders	3/66	9/70
GASTROINTESTINAL DISORDERSGastrointestinal disorders	7/66	3/70
Opportunistic Infections, all organ systems, severeInfections and infestations	3/66	7/70
LUNG TRANSPLANT REJECTIONImmune system disorders	5/66	4/70
CARDIAC DISORDERSCardiac disorders	2/66	5/70
DeathInfections and infestations	3/66	4/70
TRANSPLANT REJECTIONImmune system disorders	3/66	2/70

Most frequent other events

Showing 10 of 69

Most frequent other events
Event	Placebo Group	Treatment Group
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERSRespiratory, thoracic and mediastinal disorders	38/66	42/70
GASTROINTESTINAL DISORDERSGastrointestinal disorders	35/66	41/70
LUNG TRANSPLANT REJECTIONImmune system disorders	18/66	18/70
OEDEMA PERIPHERALRespiratory, thoracic and mediastinal disorders	12/66	17/70
DYSPNOEARespiratory, thoracic and mediastinal disorders	10/66	16/70
FATIGUERespiratory, thoracic and mediastinal disorders	13/66	15/70
ANAEMIABlood and lymphatic system disorders	5/66	15/70
coughRespiratory, thoracic and mediastinal disorders	14/66	8/70
DIARRHOEAGastrointestinal disorders	13/66	14/70
LEUKOPENIABlood and lymphatic system disorders	5/66	14/70

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Placebo Group	Treatment Group	Total
Age	50.6 ± 13.8	51.9 ± 12.2	51.3 ± 13.0

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo Group	Treatment Group	Total
Female	28	41	69
Male	38	29	67

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Placebo Group	Treatment Group	Total
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	6	7	13
White	60	63	123
More than one race	0	0	0
Unknown or Not Reported	0	0	0

FEV1, liters
FEV1, liters(liters)	Placebo Group	Treatment Group	Total
Median	0.75 (0.53 to 1.32)	0.80 (0.64 to 1.23)	0.79 (0.57 to 1.24)

Indication for Lung Transplant
Indication for Lung Transplant(subjects)	Placebo Group	Treatment Group	Total
COPD	35	33	68
Idiopathic Pulmonary Fibrosis	16	16	32
Cystic Fibrosis	11	12	23
Sarcoid	2	3	5
Other	2	6	8

FVC, liters
FVC, liters(liters)	Placebo Group	Treatment Group	Total
Median	2.02 (1.52 to 2.62)	1.89 (1.49 to 2.32)	1.95 (1.51 to 2.48)

6MWD, feet
6MWD, feet(feet)	Placebo Group	Treatment Group	Total
Median	1168 (946 to 1350)	1120 (945 to 1380)	1155 (945 to 1380)

Smoking History
Smoking History(subjects)	Placebo Group	Treatment Group	Total
No Smoking History/Never Smoked (past or present)	22	21	43
Past Smoking History: former smokers who quit	44	49	93
Current Smoking	0	0	0

1 further baseline measures are reported on the registry.

Study locations

1 site

DukeUMC
Durham, North Carolina 27710, United States

References and documents

Publications

Palmer SM, Limaye AP, Banks M, Gallup D, Chapman J, Lawrence EC, Dunitz J, Milstone A, Reynolds J, Yung GL, Chan KM, Aris R, Garrity E, Valentine V, McCall J, Chow SC, Davis RD, Avery R. Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial. Ann Intern Med. 2010 Jun 15;152(12):761-9. doi: 10.7326/0003-4819-152-12-201006150-00003. PubMed 20547904 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Oct 4, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00227370
Lead sponsor: Duke University
Collaborators: Roche Pharma AG
Responsible party: Sponsor
First posted: Sep 28, 2005
Start date: Jul 2003
Primary completion: Apr 2008
Completion: Dec 2008
Results posted: Apr 29, 2013
Last update: Oct 4, 2024

Study contacts

Scott M Palmer, MD

principal investigator · Duke University

View the source record on ClinicalTrials.gov ↗

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