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Trial record 1 of 2 for:    ceftriaxone and ALS
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Clinical Trial Ceftriaxone in Subjects With ALS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00349622
Recruitment Status : Completed
First Posted : July 7, 2006
Results First Posted : April 1, 2014
Last Update Posted : April 21, 2014
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions: Amyotrophic Lateral Sclerosis
ALS
Interventions: Drug: ceftriaxone
Other: placebo

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Ceftriaxone is approved by the U.S. Food and Drug Administration (FDA) for treating bacterial infections but not for treating ALS. Subjects with ALS were enrolled in 58 institutions across in the US and Canada.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomly assigned to receive treatment with ceftriaxone or placebo for at least 12 months. Two thirds of participants received ceftriaxone and one third received placebo. This is a blinded study, so neither participants nor study staff knew which treatment a participant is receiving.

Reporting Groups
  Description
Ceftriaxone

Two thirds of participants were assigned to 4 grams of ceftriaxone per day. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Ceftriaxone is a cephalosporin antibiotic and was administered intravenously via a central venous catheter twice a day.

Placebo

One third of participants were assigned to placebo, or an inactive substance. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Pediatric multivitamin solution was used as the placebo in this study and was administered intravenously via a central venous catheter twice a day.


Participant Flow:   Overall Study
    Ceftriaxone   Placebo
STARTED   340   173 
COMPLETED   162   77 
NOT COMPLETED   178   96 
Death                168                86 
Lost to Follow-up                5                1 
Withdrawal by Subject                5                9 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ceftriaxone

Two thirds of participants were assigned to 4 grams of ceftriaxone per day. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Ceftriaxone is a cephalosporin antibiotic and was administered intravenously via a central venous catheter twice a day.

Placebo

One third of participants were assigned to placebo, or an inactive substance. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Pediatric multivitamin solution was used as the placebo in this study and was administered intravenously via a central venous catheter twice a day.

Total Total of all reporting groups

Baseline Measures
   Ceftriaxone   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 340   173   513 
Age 
[Units: Years]
Mean (Standard Deviation)
     
Age at Screening   55.6  (10.4)   54.8  (10.3)   55.4  (10.4) 
Gender 
[Units: Participants]
     
Female   131   72   203 
Male   209   101   310 
Ethnicity (NIH/OMB) 
[Units: Participants]
     
Hispanic or Latino   17   6   23 
Not Hispanic or Latino   320   165   485 
Unknown or Not Reported   3   2   5 
Race (NIH/OMB) 
[Units: Participants]
     
American Indian or Alaska Native   2   0   2 
Asian   6   5   11 
Native Hawaiian or Other Pacific Islander   1   0   1 
Black or African American   8   3   11 
White   320   163   483 
More than one race   2   0   2 
Unknown or Not Reported   1   2   3 
Region of Enrollment 
[Units: Participants]
     
United States   293   151   444 
Canada   47   22   69 
ALS Family History [1] 
[Units: Participants]
     
Familial History of ALS   26   8   34 
No Known Familial History of ALS   307   161   468 
Unknown   7   4   11 
[1] Subjects were asked at screening whether or not they have a familial history of ALS.
Site of Onset [1] 
[Units: Participants]
     
Limb   257   137   394 
Bulbar   75   35   110 
Both   8   1   9 
[1] Indicates region of first symptoms
Riluzole Use [1] 
[Units: Participants]
     
On Riluzole   249   128   377 
Not on Riluzole   91   45   136 
[1] At the screening visit, subjects were asked whether or not they were taking a continuous dose of riluzole.
Vital Capacity Percent Predicted [1] 
[Units: Percent predicted based on age and heigh]
Mean (Standard Deviation)
 87.9  (16.6)   91.1  (18.4)   89.0  (17.3) 
[1] The vital capacity (lung capacity) for each subject was measured at screening.
Time to Screening 
[Units: Years]
Mean (Standard Deviation)
     
Years from Symptom Onset to Screening   1.49  (0.68)   1.50  (0.67)   1.49  (0.68) 
Years from Diagnosis to Screening   0.56  (0.49)   0.58  (0.49)   0.57  (0.49) 
Years from Symptom Onset to Diagnosis   0.93  (0.55)   0.92  (0.58)   0.92  (0.56) 


  Outcome Measures

1.  Primary:   Survival   [ Time Frame: From date of randomization until date of death, tracheostomy, or the initiation of permanent assisted ventilation (PAV). This was assessed at time of each participant's drug discontinuation and every 2 months thereafter for the life of the study (6 yrs) ]

Measure Type Primary
Measure Title Survival
Measure Description Survival is presented as median day of survival for each group. Survival is defined as time to death, tracheostomy or the initiation of permanent assisted ventilation (PAV).
Time Frame From date of randomization until date of death, tracheostomy, or the initiation of permanent assisted ventilation (PAV). This was assessed at time of each participant's drug discontinuation and every 2 months thereafter for the life of the study (6 yrs)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ceftriaxone

Two thirds of participants were assigned to 4 grams of ceftriaxone per day. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Ceftriaxone is a cephalosporin antibiotic and was administered intravenously via a central venous catheter twice a day.

Placebo

One third of participants were assigned to placebo, or an inactive substance. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Pediatric multivitamin solution was used as the placebo in this study and was administered intravenously via a central venous catheter twice a day.


Measured Values
   Ceftriaxone   Placebo 
Participants Analyzed 
[Units: Participants]
 340   173 
Survival 
[Units: Days]
Median (95% Confidence Interval)
 664 
 (614 to 794) 
 581 
 (521 to 672) 

No statistical analysis provided for Survival



2.  Primary:   Change From Baseline in ALS Functional Rating Scale, Revised (ALSFRS-R) at One Year   [ Time Frame: Every 8 weeks for one year ]

Measure Type Primary
Measure Title Change From Baseline in ALS Functional Rating Scale, Revised (ALSFRS-R) at One Year
Measure Description

Amyotrophic Lateral Sclerosis Functional Rating Scale, Revised (ALSFRS-R) is a quickly administered (five minute) ordinal rating scale used to determine patients' assessment of their capability and independence in 12 functional activities/questions. The 12 functional activities/questions are rated on a scale of 0 to 4 for a total scoring range of 0-48, with 48 representing optimal function. All 12 activities are relevant in ALS.

This outcome measure calculation is based on measurements every 8 weeks from the Baseline Visit up until one year.

Time Frame Every 8 weeks for one year  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ceftriaxone

Two thirds of participants were assigned to 4 grams of ceftriaxone per day. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Ceftriaxone is a cephalosporin antibiotic and was administered intravenously via a central venous catheter twice a day.

Placebo

One third of participants were assigned to placebo, or an inactive substance. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Pediatric multivitamin solution was used as the placebo in this study and was administered intravenously via a central venous catheter twice a day.


Measured Values
   Ceftriaxone   Placebo 
Participants Analyzed 
[Units: Participants]
 340   173 
Change From Baseline in ALS Functional Rating Scale, Revised (ALSFRS-R) at One Year 
[Units: Units on a scale per 8 weeks]
Mean (Standard Error)
 -1.1311  (0.04395)   -1.2208  (0.06177) 

No statistical analysis provided for Change From Baseline in ALS Functional Rating Scale, Revised (ALSFRS-R) at One Year



3.  Secondary:   Change in % Vital Capacity From Screening to One Year   [ Time Frame: Every 12 weeks for one Year ]

Measure Type Secondary
Measure Title Change in % Vital Capacity From Screening to One Year
Measure Description

Vital Capacity is measured as the percent predicted per subject based on age, gender, and height, and is performed as a Slow Vital Capacity.

This outcome measure calculation is based on measurements every 12 weeks from the Baseline Visit up until one year.

Time Frame Every 12 weeks for one Year  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ceftriaxone

Two thirds of participants were assigned to 4 grams of ceftriaxone per day. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Ceftriaxone is a cephalosporin antibiotic and was administered intravenously via a central venous catheter twice a day.

Placebo

One third of participants were assigned to placebo, or an inactive substance. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Pediatric multivitamin solution was used as the placebo in this study and was administered intravenously via a central venous catheter twice a day.


Measured Values
   Ceftriaxone   Placebo 
Participants Analyzed 
[Units: Participants]
 340   173 
Change in % Vital Capacity From Screening to One Year 
[Units: Percent change in VC per 12 weeks]
Mean (Standard Error)
 -2.772  (0.1417)   -3.0826  (0.1970) 

No statistical analysis provided for Change in % Vital Capacity From Screening to One Year



4.  Secondary:   Change From Baseline in Evaluation of Multiple Upper Extremity Muscles Using Hand Held Dynamometry at One Year   [ Time Frame: Every 12 weeks for one Year ]

Measure Type Secondary
Measure Title Change From Baseline in Evaluation of Multiple Upper Extremity Muscles Using Hand Held Dynamometry at One Year
Measure Description

Hand-held Dynamometry (HHD) is used to evaluate muscle strength. Six proximal muscle groups were examined bilaterally in both upper and lower extremities (shoulder flexion, elbow flexion, elbow extension, hip flexion, knee flexion, and knee extension). In addition, wrist extension, first dorsal interosseous contraction and ankle dorsiflexion were measured bilaterally.

HHD analysis was performed using Percent Change from Baseline. Each subject’s baseline strength value for each muscle group is considered 100%. During successive visits strength for each muscle group was measured using HHD and was calculated as a percentage of the initial baseline value recorded. Upper extremity and lower extremity values were calculated as the sum of all tests for that extremity to create one megascore for upper and one megascore for lower extremity muscles.

This outcome measure calculation is based on measurements every 12 weeks from the Baseline Visit up until one year.

Time Frame Every 12 weeks for one Year  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ceftriaxone

Two thirds of participants were assigned to 4 grams of ceftriaxone per day. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Ceftriaxone is a cephalosporin antibiotic and was administered intravenously via a central venous catheter twice a day.

Placebo

One third of participants were assigned to placebo, or an inactive substance. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Pediatric multivitamin solution was used as the placebo in this study and was administered intravenously via a central venous catheter twice a day.


Measured Values
   Ceftriaxone   Placebo 
Participants Analyzed 
[Units: Participants]
 340   173 
Change From Baseline in Evaluation of Multiple Upper Extremity Muscles Using Hand Held Dynamometry at One Year 
[Units: Percent change per 12 weeks]
Mean (Standard Error)
 -5.2735  (0.2178)   -5.5526  (0.3040) 

No statistical analysis provided for Change From Baseline in Evaluation of Multiple Upper Extremity Muscles Using Hand Held Dynamometry at One Year



5.  Secondary:   Change From Baseline in the ALS-Specific Quality of Life Scale (ALSQOL) at One Year   [ Time Frame: Every 12 weeks for one Year ]

Measure Type Secondary
Measure Title Change From Baseline in the ALS-Specific Quality of Life Scale (ALSQOL) at One Year
Measure Description

The ALS-Specific Quality of Life Scale (ALSQOL). was developed, tested, and validated in subjects with ALS, and is not a health-related quality of life scale. The scale consists of 59 questions that ask about severity of the symptoms of ALS, mood and affect, intimacy, and social issues. Each question for the ALSQOL is scored from 0-10. With 59 questions, total score ranges from 0-590 with scores simply added, with 590 representing highest quality of life. However since 10 is maximally weighted towards negative values on some questions and positive values on others, the following questions must have results transposed (Simply reverse the scale, for instance 10=0 and 0=10) prior to analysis: 1-10, 11, 16, 19, 24, 26, 28, 32, 35, 36, 38, and 41. Optional items are 50, 53, 56, and 59. These questions are not included on any scale or in any quantitative analyses.

This outcome measure calculation is based on measurements every 12 weeks from the Baseline Visit up until one year.

Time Frame Every 12 weeks for one Year  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ceftriaxone

Two thirds of participants were assigned to 4 grams of ceftriaxone per day. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Ceftriaxone is a cephalosporin antibiotic and was administered intravenously via a central venous catheter twice a day.

Placebo

One third of participants were assigned to placebo, or an inactive substance. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Pediatric multivitamin solution was used as the placebo in this study and was administered intravenously via a central venous catheter twice a day.


Measured Values
   Ceftriaxone   Placebo 
Participants Analyzed 
[Units: Participants]
 340   173 
Change From Baseline in the ALS-Specific Quality of Life Scale (ALSQOL) at One Year 
[Units: Units on a scale per 12 weeks]
Mean (Standard Error)
 -3.5084  (0.3297)   -3.4401  (0.4629) 

No statistical analysis provided for Change From Baseline in the ALS-Specific Quality of Life Scale (ALSQOL) at One Year



6.  Secondary:   Change From Baseline in Evaluation of Multiple Lower Extremity Muscles Using Hand Held Dynamometry at One Year   [ Time Frame: Every 12 weeks for one Year ]

Measure Type Secondary
Measure Title Change From Baseline in Evaluation of Multiple Lower Extremity Muscles Using Hand Held Dynamometry at One Year
Measure Description

Hand-held Dynamometry (HHD) is used to evaluate muscle strength. Six proximal muscle groups were examined bilaterally in both upper and lower extremities (shoulder flexion, elbow flexion, elbow extension, hip flexion, knee flexion, and knee extension). In addition, wrist extension, first dorsal interosseous contraction and ankle dorsiflexion were measured bilaterally.

HHD analysis was performed using Percent Change from Baseline. Each subject’s baseline strength value for each muscle group is considered 100%. During successive visits strength for each muscle group was measured using HHD and was calculated as a percentage of the initial baseline value recorded. Upper extremity and lower extremity values were calculated as the sum of all tests for that extremity to create one megascore for upper and one megascore for lower extremity muscles.

This outcome measure calculation is based on measurements every 12 weeks from the Baseline Visit up until one year.

Time Frame Every 12 weeks for one Year  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ceftriaxone

Two thirds of participants were assigned to 4 grams of ceftriaxone per day. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Ceftriaxone is a cephalosporin antibiotic and was administered intravenously via a central venous catheter twice a day.

Placebo

One third of participants were assigned to placebo, or an inactive substance. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.

Pediatric multivitamin solution was used as the placebo in this study and was administered intravenously via a central venous catheter twice a day.


Measured Values
   Ceftriaxone   Placebo 
Participants Analyzed 
[Units: Participants]
 340   173 
Change From Baseline in Evaluation of Multiple Lower Extremity Muscles Using Hand Held Dynamometry at One Year 
[Units: Percent change per 12 weeks]
Mean (Standard Error)
 -4.1530  (0.2591)   -4.4807  (0.3625) 

No statistical analysis provided for Change From Baseline in Evaluation of Multiple Lower Extremity Muscles Using Hand Held Dynamometry at One Year




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

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: Merit Cudkowicz
Organization: MGH
phone: 617-724-1873
e-mail: mcudkowicz@partners.org


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Merit E. Cudkowicz, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00349622     History of Changes
Other Study ID Numbers: U01NS049640-02 ( U.S. NIH Grant/Contract )
NINDS ( Other Identifier: NINDS )
NINDS CRC ( Other Identifier: NINDS Clinical Research Collaboration )
First Submitted: July 5, 2006
First Posted: July 7, 2006
Results First Submitted: October 23, 2013
Results First Posted: April 1, 2014
Last Update Posted: April 21, 2014