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Trial record 23 of 101 for:    Valcyte

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

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ClinicalTrials.gov Identifier: NCT00227370
Recruitment Status : Completed
First Posted : September 28, 2005
Results First Posted : April 29, 2013
Last Update Posted : April 29, 2013
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Scott Palmer, Duke University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Prevention
Condition Cytomegalovirus Infections
Interventions Drug: valganciclovir
Other: Placebo
Enrollment 136
Recruitment Details 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.
Pre-assignment Details Upon receipt of a lung transplant, enrolled subjects received 90 days of valganciclovir for CMV prophylaxis, per standard of care, and then were randomly assigned, 1:1, in a double blind fashion, to either the extended prophylaxis group (9 additional months of standard of care dosing Valganciclovir, adjusted for renal function) or placebo group.
Arm/Group Title Placebo Group Treatment Group
Hide Arm/Group Description Upon randomization at 3 months, patients discontinued Valganciclovir and received no CMV prophylaxis for the next 9 months (short course prophylaxis). 3 months of Valganciclovir was the standard of care for CMV prevention at the time of study initiation. This was the prespecified placebo group/intervention arm. Upon randomization at 3 months, patients remained on Valganciclovir for 9 additional months (extended course prophylaxis).
Period Title: Overall Study
Started 66 [1] 70 [2]
Completed 45 46
Not Completed 21 24
Reason Not Completed
Withdrawal by Subject             1             2
Death             3             4
Adverse Event             6             11
Physician Decision             9             6
Other reasons             2             1
[1]
Placebo Group
[2]
Treatment Group
Arm/Group Title Placebo Group Treatment Group Total
Hide Arm/Group Description Upon randomisation at 3 months, patients discontinued Valganciclovir and received no CMV prophylaxis Upon randomisation at 3 months, patients remained on Valganciclovir for 9 additional months. Total of all reporting groups
Overall Number of Baseline Participants 66 70 136
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Age Number Analyzed 66 participants 70 participants 136 participants
50.6  (13.8) 51.9  (12.2) 51.3  (13.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 70 participants 136 participants
Female
28
  42.4%
41
  58.6%
69
  50.7%
Male
38
  57.6%
29
  41.4%
67
  49.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 70 participants 136 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
   9.1%
7
  10.0%
13
   9.6%
White
60
  90.9%
63
  90.0%
123
  90.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
FEV1, liters   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Liters
Number Analyzed 66 participants 70 participants 136 participants
0.75
(0.53 to 1.32)
0.80
(0.64 to 1.23)
0.79
(0.57 to 1.24)
[1]
Measure Description: Forced Expiratory Volume in 1 second, liters
Indication for Lung Transplant   [1] 
Measure Type: Number
Unit of measure:  Subjects
Number Analyzed 66 participants 70 participants 136 participants
COPD 35 33 68
Idiopathic Pulmonary Fibrosis 16 16 32
Cystic Fibrosis 11 12 23
Sarcoid 2 3 5
Other 2 6 8
[1]
Measure Description:

Placebo Group: Treatment Group:

COPD: 35 33 Cystic Fibrosis: 11 12 IPF: 16 16 Sarcoid: 2 3 Other: 2 6

FVC, liters   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Liters
Number Analyzed 66 participants 70 participants 136 participants
2.02
(1.52 to 2.62)
1.89
(1.49 to 2.32)
1.95
(1.51 to 2.48)
[1]
Measure Description: forced vital capacity
6MWD, feet   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Feet
Number Analyzed 66 participants 70 participants 136 participants
1168
(946 to 1350)
1120
(945 to 1380)
1155
(945 to 1380)
[1]
Measure Description: the distance in feet a subject walks in 6 minutes
Smoking History   [1] 
Measure Type: Number
Unit of measure:  Subjects
Number Analyzed 66 participants 70 participants 136 participants
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]
Measure Description: Placebo Treatment Past:44/66 49/70 Current: 0 0 No hx:22/66 21/70
Daily Supplemental Oxygen Use   [1] 
Measure Type: Number
Unit of measure:  Subjects
Number Analyzed 66 participants 70 participants 136 participants
Supplemental Oxygen use 53 51 104
No supplemental oxygen use 13 19 32
[1]
Measure Description: the number of subjects requiring supplemental daily oxygen through nasal canula or face mask.
1.Primary Outcome
Title Incidence of CMV End Organ Disease
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat analysis was conducted.
Arm/Group Title Placebo Group Treatment Group
Hide Arm/Group Description:
Upon randomization at 3 months, patients discontinued Valganciclovir and received no CMV prophylaxis for the next 9 months (short course prophylaxis)
Upon randomization at 3 months, patients remained on Valganciclovir for 9 additional months (extended course prophylaxis).
Overall Number of Participants Analyzed 66 70
Measure Type: Number
Unit of Measure: participants
21 1
2.Primary Outcome
Title Incidence of CMV Syndrome
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
intention to treat analysis
Arm/Group Title Placebo Group Treatment Group
Hide Arm/Group Description:
Upon randomization at 3 months, patients discontinued Valganciclovir and received no CMV prophylaxis for the next 9 months (short course prophylaxis)
Upon randomization at 3 months, patients remained on Valganciclovir for 9 additional months (extended course prophylaxis).
Overall Number of Participants Analyzed 66 70
Measure Type: Number
Unit of Measure: participants
13 0
3.Secondary Outcome
Title Any CMV Infection
Hide Description Inclusive of CMV syndrome, disease, or infection not meeting primary end point.
Time Frame over the course of 300 days post randomization
Hide Outcome Measure Data
Hide Analysis Population Description
intention to treat
Arm/Group Title Placebo Group Treatment Group
Hide Arm/Group Description:
Upon randomization at 3 months, patients discontinued Valganciclovir and received no CMV prophylaxis for the next 9 months (short course prophylaxis)
Upon randomization at 3 months, patients remained on Valganciclovir for 9 additional months (extended course prophylaxis).
Overall Number of Participants Analyzed 66 70
Measure Type: Number
Unit of Measure: participants
42 7
4.Secondary Outcome
Title Biopsy Proven Acute Lung Rejection
Hide Description [Not Specified]
Time Frame over the course of 300 days of randomization
Hide Outcome Measure Data
Hide Analysis Population Description
intention to treat
Arm/Group Title Placebo Group Treatment Group
Hide Arm/Group Description:
Upon randomization at 3 months, patients discontinued Valganciclovir and received no CMV prophylaxis for the next 9 months (short course prophylaxis)
Upon randomization at 3 months, patients remained on Valganciclovir for 9 additional months (extended course prophylaxis).
Overall Number of Participants Analyzed 66 70
Measure Type: Number
Unit of Measure: participants
22 15
5.Secondary Outcome
Title Non-CMV Infection
Hide Description non cmv opportunistic infections
Time Frame over the course of 300 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
intention to treat
Arm/Group Title Placebo Group Treatment Group
Hide Arm/Group Description:
Upon randomization at 3 months, patients discontinued Valganciclovir and received no CMV prophylaxis for the next 9 months (short course prophylaxis)
Upon randomization at 3 months, patients remained on Valganciclovir for 9 additional months (extended course prophylaxis).
Overall Number of Participants Analyzed 66 70
Measure Type: Number
Unit of Measure: participants
35 38
6.Secondary Outcome
Title Severity of Viremia
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
intention to treat
Arm/Group Title Placebo Group Treatment Group
Hide Arm/Group Description:
Upon randomization at 3 months, patients discontinued Valganciclovir and received no CMV prophylaxis for the next 9 months (short course prophylaxis)
Upon randomization at 3 months, patients remained on Valganciclovir for 9 additional months (extended course prophylaxis).
Overall Number of Participants Analyzed 66 70
Median (Inter-Quartile Range)
Unit of Measure: CMV copies/mL
110000
(40000 to 361569)
3200
(2700 to 3700)
7.Secondary Outcome
Title Ganciclovir Resistance
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
intention to treat
Arm/Group Title Placebo Group Treatment Group
Hide Arm/Group Description:
Upon randomization at 3 months, patients discontinued Valganciclovir and received no CMV prophylaxis for the next 9 months (short course prophylaxis)
Upon randomization at 3 months, patients remained on Valganciclovir for 9 additional months (extended course prophylaxis).
Overall Number of Participants Analyzed 66 70
Measure Type: Number
Unit of Measure: participants
1 2
Time Frame 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).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Group Treatment Group
Hide Arm/Group Description Upon randomization at 3 months, patients discontinued Valganciclovir and received no CMV prophylaxis for the next 9 months (short course prophylaxis) Upon randomization at 3 months, patients remained on Valganciclovir for 9 additional months (extended course prophylaxis).
All-Cause Mortality
Placebo Group Treatment Group
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Group Treatment Group
Affected / at Risk (%) Affected / at Risk (%)
Total   35/66 (53.03%)   38/70 (54.29%) 
Blood and lymphatic system disorders     
ANAEMIA  1  1/66 (1.52%)  2/70 (2.86%) 
ISCHAEMIC STROKE  1  0/66 (0.00%)  1/70 (1.43%) 
Cardiac disorders     
CARDIAC DISORDERS  1  2/66 (3.03%)  5/70 (7.14%) 
CARDIAC ARREST  1  1/66 (1.52%)  0/70 (0.00%) 
Hospitalization  1  0/66 (0.00%)  1/70 (1.43%) 
Gastrointestinal disorders     
GASTROENTERITIS  1  0/66 (0.00%)  3/70 (4.29%) 
CLOSTRIDIUM DIFFICILE COLITIS  1  1/66 (1.52%)  0/70 (0.00%) 
GASTROINTESTINAL DISORDERS  1  7/66 (10.61%)  3/70 (4.29%) 
ABDOMINAL PAIN  1  1/66 (1.52%)  1/70 (1.43%) 
VOMITING  1  1/66 (1.52%)  1/70 (1.43%) 
GASTROINTESTINAL DISORDER  1  1/66 (1.52%)  0/70 (0.00%) 
INTESTINAL OBSTRUCTION  1  1/66 (1.52%)  0/70 (0.00%) 
PYREXIA  1  1/66 (1.52%)  3/70 (4.29%) 
General disorders     
ACUTE RESPIRATORY DISTRESS SYNDROME  1  0/66 (0.00%)  1/70 (1.43%) 
BRONCHOSTENOSIS  1  0/66 (0.00%)  1/70 (1.43%) 
MULTI-ORGAN FAILURE  1  0/66 (0.00%)  1/70 (1.43%) 
HEADACHE  1  0/66 (0.00%)  1/70 (1.43%) 
Immune system disorders     
LUNG TRANSPLANT REJECTION  1  5/66 (7.58%)  4/70 (5.71%) 
TRANSPLANT REJECTION  1  3/66 (4.55%)  2/70 (2.86%) 
NEUTROPENIA  1  3/66 (4.55%)  9/70 (12.86%) 
Infections and infestations     
SEPSIS  1  0/66 (0.00%)  1/70 (1.43%) 
CYTOMEGALOVIRUS COLITIS  1  1/66 (1.52%)  0/70 (0.00%) 
WOUND INFECTION  1  1/66 (1.52%)  0/70 (0.00%) 
PLEURAL EFFUSION  1  2/66 (3.03%)  0/70 (0.00%) 
RESPIRATORY FAILURE  1  1/66 (1.52%)  1/70 (1.43%) 
LUNG INFILTRATION  1  0/66 (0.00%)  1/70 (1.43%) 
Opportunistic Infections, all organ systems  1  31/66 (46.97%)  32/70 (45.71%) 
Opportunistic Infections, all organ systems, mild  1  11/66 (16.67%)  8/70 (11.43%) 
Opportunistic Infections, all organ systems, moderate  1  17/66 (25.76%)  17/70 (24.29%) 
Opportunistic Infections, all organ systems, severe  1  3/66 (4.55%)  7/70 (10.00%) 
Death  1  3/66 (4.55%)  4/70 (5.71%) 
Respiratory, thoracic and mediastinal disorders     
PULMONARY HAEMORRHAGE  1  0/66 (0.00%)  1/70 (1.43%) 
Vascular disorders     
ENCEPHALOPATHY  1  0/66 (0.00%)  2/70 (2.86%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Group Treatment Group
Affected / at Risk (%) Affected / at Risk (%)
Total   64/66 (96.97%)   70/70 (100.00%) 
Blood and lymphatic system disorders     
ANAEMIA  1  5/66 (7.58%)  15/70 (21.43%) 
LEUKOPENIA  1  5/66 (7.58%)  14/70 (20.00%) 
NEUTROPENIA  1  3/66 (4.55%)  9/70 (12.86%) 
THROMBOCYTOPENIA  1  1/66 (1.52%)  4/70 (5.71%) 
Eye disorders     
VISION BLURRED  1  3/66 (4.55%)  4/70 (5.71%) 
Gastrointestinal disorders     
GASTROINTESTINAL DISORDERS  1  35/66 (53.03%)  41/70 (58.57%) 
DIARRHOEA  1  13/66 (19.70%)  14/70 (20.00%) 
VOMITING  1  9/66 (13.64%)  11/70 (15.71%) 
NAUSEA  1  7/66 (10.61%)  11/70 (15.71%) 
ABDOMINAL PAIN  1  4/66 (6.06%)  8/70 (11.43%) 
GASTROOESOPHAGEAL REFLUX DISEASE  1  4/66 (6.06%)  8/70 (11.43%) 
ABDOMINAL DISTENSION  1  5/66 (7.58%)  5/70 (7.14%) 
CONSTIPATION  1  6/66 (9.09%)  4/70 (5.71%) 
Immune system disorders     
LUNG TRANSPLANT REJECTION  1  18/66 (27.27%)  18/70 (25.71%) 
TRANSPLANT REJECTION  1  5/66 (7.58%)  4/70 (5.71%) 
Investigations     
WEIGHT INCREASED  1  6/66 (9.09%)  6/70 (8.57%) 
PULMONARY FUNCTION TEST DECREASED  1  2/66 (3.03%)  4/70 (5.71%) 
HEPATIC ENZYME INCREASED  1  1/66 (1.52%)  4/70 (5.71%) 
BREATH SOUNDS ABNORMAL  1  0/66 (0.00%)  4/70 (5.71%) 
Metabolism and nutrition disorders     
HYPERKALAEMIA  1  6/66 (9.09%)  1/70 (1.43%) 
HYPOMAGNESAEMIA  1  2/66 (3.03%)  4/70 (5.71%) 
DECREASED APPETITE  1  1/66 (1.52%)  4/70 (5.71%) 
DEHYDRATION  1  4/66 (6.06%)  1/70 (1.43%) 
HYPERGLYCAEMIA  1  4/66 (6.06%)  1/70 (1.43%) 
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  7/66 (10.61%)  6/70 (8.57%) 
PAIN IN EXTREMITY  1  10/66 (15.15%)  3/70 (4.29%) 
BACK PAIN  1  5/66 (7.58%)  4/70 (5.71%) 
MUSCLE SPASMS  1  2/66 (3.03%)  6/70 (8.57%) 
MUSCULAR WEAKNESS  1  5/66 (7.58%)  3/70 (4.29%) 
Nervous system disorders     
HEADACHE  1  12/66 (18.18%)  11/70 (15.71%) 
TREMOR  1  7/66 (10.61%)  4/70 (5.71%) 
DIZZINESS  1  4/66 (6.06%)  5/70 (7.14%) 
HYPOAESTHESIA  1  2/66 (3.03%)  4/70 (5.71%) 
MIGRAINE  1  4/66 (6.06%)  0/70 (0.00%) 
SINUS HEADACHE  1  4/66 (6.06%)  0/70 (0.00%) 
Psychiatric disorders     
INSOMNIA  1  7/66 (10.61%)  4/70 (5.71%) 
DEPRESSION  1  4/66 (6.06%)  4/70 (5.71%) 
Renal and urinary disorders     
RENAL FAILURE  1  0/66 (0.00%)  10/70 (14.29%) 
RENAL FAILURE ACUTE  1  3/66 (4.55%)  5/70 (7.14%) 
Respiratory, thoracic and mediastinal disorders     
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS  1  38/66 (57.58%)  42/70 (60.00%) 
DYSPNOEA  1  10/66 (15.15%)  16/70 (22.86%) 
cough  1  14/66 (21.21%)  8/70 (11.43%) 
DYSPNOEA EXERTIONAL  1  7/66 (10.61%)  11/70 (15.71%) 
PRODUCTIVE COUGH  1  7/66 (10.61%)  11/70 (15.71%) 
PLEURAL EFFUSION  1  6/66 (9.09%)  6/70 (8.57%) 
RHINORRHOEA  1  5/66 (7.58%)  5/70 (7.14%) 
WHEEZING  1  3/66 (4.55%)  7/70 (10.00%) 
OROPHARYNGEAL PAIN  1  4/66 (6.06%)  4/70 (5.71%) 
LUNG INFILTRATION  1  2/66 (3.03%)  4/70 (5.71%) 
PNEUMOTHORAX  1  2/66 (3.03%)  4/70 (5.71%) 
BRONCHOSTENOSIS  1  0/66 (0.00%)  5/70 (7.14%) 
OEDEMA PERIPHERAL  1  12/66 (18.18%)  17/70 (24.29%) 
FATIGUE  1  13/66 (19.70%)  15/70 (21.43%) 
PYREXIA  1  11/66 (16.67%)  7/70 (10.00%) 
CHEST PAIN  1  8/66 (12.12%)  6/70 (8.57%) 
CHEST DISCOMFORT  1  3/66 (4.55%)  6/70 (8.57%) 
MALAISE  1  4/66 (6.06%)  3/70 (4.29%) 
OEDEMA  1  4/66 (6.06%)  3/70 (4.29%) 
CHILLS  1  4/66 (6.06%)  2/70 (2.86%) 
ASTHENIA  1  0/66 (0.00%)  4/70 (5.71%) 
GENERALISED OEDEMA  1  3/66 (4.55%)  0/70 (0.00%) 
UPPER RESPIRATORY TRACT INFECTION  1  12/66 (18.18%)  10/70 (14.29%) 
PNEUMONIA  1  9/66 (13.64%)  4/70 (5.71%) 
SINUSITIS  1  6/66 (9.09%)  6/70 (8.57%) 
BRONCHITIS  1  2/66 (3.03%)  4/70 (5.71%) 
SEPSIS  1  1/66 (1.52%)  4/70 (5.71%) 
Skin and subcutaneous tissue disorders     
ALOPECIA  1  6/66 (9.09%)  4/70 (5.71%) 
rash  1  6/66 (9.09%)  0/70 (0.00%) 
Vascular disorders     
HYPERTENSION  1  7/66 (10.61%)  11/70 (15.71%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Scott M. Palmer, MD, MHS
Organization: Duke Clinical Research Institute
Phone: 919 684 0254
Responsible Party: Scott Palmer, Duke University
ClinicalTrials.gov Identifier: NCT00227370     History of Changes
Other Study ID Numbers: Pro00013245
4623 (Val038) ( Other Identifier: Alternative study ID )
First Submitted: September 26, 2005
First Posted: September 28, 2005
Results First Submitted: January 24, 2013
Results First Posted: April 29, 2013
Last Update Posted: April 29, 2013