HIV-associated Cognitive Impairment, HIV Infections
Conditions
Keywords
Human immunodeficiency virus (HIV), HIV associated cognitive impairment, HIV dementia, Uganda, Acquired immune deficiency syndrome (AIDS), Treatment Naive
Brief summary
Purpose: The purpose of the study is to assess the safety and effectiveness of minocycline, an antibiotic, in the treatment of Human immunodeficiency virus (HIV)-associated cognitive impairment in Uganda. Study Design: Treatment, 24-week Randomized, Placebo-Controlled, Double-Blind Phase with Optional 24-week Open Label Phase for Subjects with a cluster of differentiation 4 (CD4) Count in the 251-350 Range * Arm 1: Minocycline 100 mg orally every 12 hours (50 subjects) * Arm 2: Matching placebo orally every 12 hours (50 subjects) Primary Objective: · To examine whether minocycline treatment will improve cognitive performance after 24 weeks compared to baseline Secondary Objectives: * To examine whether minocycline treatment for 24 weeks is safe and well-tolerated in individuals with HIV-associated cognitive impairment * To examine whether minocycline treatment for 48 weeks is safe and well-tolerated in individuals with HIV-associated cognitive impairment * To examine whether minocycline treatment for 24 weeks improves functional impairment
Interventions
DRUGminocycline
100 mg capsule every 12 hours by mouth
DRUGminocycline placebo capsule
1 capsule every 12 hours by mouth
Sponsors
Makerere University
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* HIV infection prior to study entry * Naïve to any antiretroviral regimen and ineligible to receive antiretroviral therapy by cluster of differentiation 4 (CD4) criteria in Uganda * Negative serum or urine pregnancy test for women of childbearing potential * Willingness to use birth control * Age 18-65 years * AIDS Dementia Scale Stage 0.5 OR 1 * Impaired cognitive performance as evidenced by an International HIV Dementia Scale (HDS) as defined by the protocol * Ability to sit or stand and swallow intact capsules with an 8-ounce glass of water * Ability and willingness of subject or legal guardian/ representative to give written informed consent * Resident within a 20km radius of Kampala city
Exclusion criteria
* Current cancers other than basal cell carcinoma, in situ carcinoma of the cervix, or Kaposi's sarcoma without evidence of visceral involvement or which does not require systemic chemotherapy * Severe premorbid psychiatric illness, including schizophrenia and major depression which, in the in investigator's opinion, is likely to interfere with study compliance * Active symptomatic AIDS-defining opportunistic infection within 45 days prior to study entry * Confounding neurological disorders as defined in the protocol * Central nervous system infections or cancers as defined in the protocol * Systemic lupus * Thyroid disease diagnosed within 24 weeks prior to entry * Breastfeeding * Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements * Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigator * History of allergy/sensitivity to minocycline or other tetracyclines and their formulations * Any other clinically significant condition or laboratory abnormality that, in the opinion of the investigator, would interfere with the subject's ability to participate in the study. This includes an individual found to have an HIV dementia scale stage 3 or 4. * Any esophageal or other condition that would interfere with the swallowing of the study medication * Use of excluded drugs as defined by the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) | At baseline and week 24 | The U NP Sum is defined as the average of z scores for 9 neuropsychological test subcomponents in the neuropsychological test battery (i.e. the average of norm-adjusted (z) scores for Grooved Pegboard Dominant Hand, Grooved Pegboard Non-dominant Hand, Color Trails 1, Color Trails 2, Symbol Digit, WHO-UCLA Verbal Learning test Trial 5, WHO-UCLA Verbal Learning test delayed recall, Digit Span forward and Digit Span backward). The outcome is defined as U NP Sum at week 24 - U NP Sum at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 24-week Change of Karnofsky Performance Score | At baseline and week 24 | The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline. |
| Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. | Time of initial Grade ≥ 2 toxicity and/or sign and symptom event up to week 24 | The outcome is the time to first Grade ≥ 2 toxicity and/or sign and symptoms from study treatment initiation up to week 24. The grade was determined by clinicians and an Grade ≥ 2 event means moderate, severe, life-threatening, or death event. |
| Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms | Time of first Grade ≥ 2 toxicity and/or sign and symptom event up to 48 weeks | The outcome is the time of first Grade ≥ 2 toxicity and/or sign and symptoms from treatment initiation up to 48 weeks. The grade was determined by clinicians and an Grade ≥ 2 event means moderate, severe, life-threatening, or death event. |
| 24-week Change of CD4 Cell Counts | At baseline and week 24 | The outcome is defined as CD4 cell count at week 24 - CD4 cell count at baseline. The unit is cells/mm\^3. |
| 24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage | At baseline and week 24 | The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline. |
| 24-week Change of Instrumental Activities of Daily Living | At baseline and week 24 | The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline. |
| 24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed) | At baseline and week 24 | The outcome is the HIV RNA plasma viral loads (Log10 transformed) at week 24 - the viral loads (Log10 transformed) at baseline. |
| 24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score | At baseline and week 24 | The outcome is the total CES-D score at week 24 - the total CES-D score at baseline. The total CES-D score is based on 20 CES-D items, such as I was bothered by things that usually don't bother me and I did not feel like eating, my appetite was poor. Patients were asked to answer each item by 4 scales: (1) Rarely, (2) Sometimes, (3) Occasionally, and (4) Most of the time. After 4 negative items were multiplied by -1, the total CES-D score is a simple sum of all items. The min and Max are 0 and 60, respectively. Higher scores indicate more severe depressive symptoms. |
| 48-week Change of CD4 Cell Counts | At baseline and week 48 | The outcome is defined as CD4 cell count at week 48 - CD4 cell count at baseline. The unit is cells/mm\^3. |
Countries
Uganda
Participant flow
Recruitment details
The recruitment period was from Mar 2008 to Oct 2009 when the study was stopped early (Data and Safety Monitoring Board (DSMB) decision based on futility) on Nov 2009. The study participants were recruited from the Infectious Disease Institute, Makerere University, Kampala, Uganda.
Pre-assignment details
Total of 353 participants were screened; only 73 were randomized and thus 280 were not enrolled: 146 of them did not have cognitive impairment, 55 of them lacked laboratory inclusion criteria, and 79 of them had others.
Participants by arm
| Arm | Count |
|---|---|
| Minocycline Minocycline 100 mg orally every 12 hours | 36 |
| Placebo Placebo minocycline capsules every 12 hours | 37 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Step1 | Adverse Event | 1 | 1 |
| Step1 | Early Study Closure | 5 | 7 |
| Step1 | Pregnancy | 1 | 0 |
| Step1 | Protocol Violation | 1 | 0 |
| Step1 | Withdrawal by Subject | 2 | 3 |
| Step2 | Adverse Event | 0 | 3 |
| Step2 | Early Study Closure | 6 | 2 |
| Step2 | Initiation of antiretroviral therapy/ART | 0 | 1 |
Baseline characteristics
| Characteristic | Minocycline | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 37 Participants | 73 Participants |
| Age Continuous | 37.3 years STANDARD_DEVIATION 8.21 | 36.7 years STANDARD_DEVIATION 7.17 | 37.0 years STANDARD_DEVIATION 7.66 |
| Baseline Cluster of Differentiation Four (CD4) Count | 319 cells/mm^3 | 305 cells/mm^3 | 313 cells/mm^3 |
| Baseline Instrumental Activities of Daily Living (IADL) Not having any difficulties on the tasks | 29 Participants | 35 Participants | 64 Participants |
| Baseline Instrumental Activities of Daily Living (IADL) Primarily cognitive problems | 1 Participants | 0 Participants | 1 Participants |
| Baseline Instrumental Activities of Daily Living (IADL) Primarily physical problems | 6 Participants | 2 Participants | 8 Participants |
| Baseline Karnofsky's Performance Score 100 (Karnofsky Score) | 0 Participants | 1 Participants | 1 Participants |
| Baseline Karnofsky's Performance Score 80 (Karnofsky Score) | 1 Participants | 2 Participants | 3 Participants |
| Baseline Karnofsky's Performance Score 90 (Karnofsky Score) | 35 Participants | 34 Participants | 69 Participants |
| Baseline Log10(Human immunodeficiency virus (HIV) Ribonucleic Acid (RNA) Viral Load (VL)) | 4.41 copies/mL | 4.59 copies/mL | 4.50 copies/mL |
| Baseline Memorial Sloan Kettering (MSK) Acquired Immune Deficiency Syndrome (AIDS) Dementia Scale Equivocal/subclinical | 35 Participants | 37 Participants | 72 Participants |
| Baseline Memorial Sloan Kettering (MSK) Acquired Immune Deficiency Syndrome (AIDS) Dementia Scale Mild | 1 Participants | 0 Participants | 1 Participants |
| Baseline Overall Neurological Assessment Can not assess | 1 Participants | 0 Participants | 1 Participants |
| Baseline Overall Neurological Assessment Central Nervous System (CNS) abnormality only | 4 Participants | 5 Participants | 9 Participants |
| Baseline Overall Neurological Assessment CNS and PNS abnormality | 1 Participants | 1 Participants | 2 Participants |
| Baseline Overall Neurological Assessment Normal neurological assessment | 26 Participants | 30 Participants | 56 Participants |
| Baseline Overall Neurological Assessment Peripheral Nervous System (PNS) abnormality only | 4 Participants | 1 Participants | 5 Participants |
| Baseline Uganda Neuropsychological Test Battery Summary measure (U NP Sum) | -0.97 z-scores STANDARD_DEVIATION 0.78 | -0.97 z-scores STANDARD_DEVIATION 0.86 | -0.97 z-scores STANDARD_DEVIATION 0.82 |
| Color Trails 1 | -1.35 z-scores STANDARD_DEVIATION 2.03 | -1.65 z-scores STANDARD_DEVIATION 3.03 | -1.51 z-scores STANDARD_DEVIATION 2.6 |
| Color Trails 2 | -2.55 z-scores STANDARD_DEVIATION 2.07 | -2.33 z-scores STANDARD_DEVIATION 2.05 | -2.44 z-scores STANDARD_DEVIATION 2.05 |
| Digit Span Backward | -0.68 z-scores STANDARD_DEVIATION 0.75 | -0.94 z-scores STANDARD_DEVIATION 1.06 | -0.81 z-scores STANDARD_DEVIATION 0.93 |
| Digit Span Forward | 0.02 z-scores STANDARD_DEVIATION 0.79 | 0.19 z-scores STANDARD_DEVIATION 0.99 | 0.11 z-scores STANDARD_DEVIATION 0.9 |
| Grooved Pegboard Dominant | -0.34 z-scores STANDARD_DEVIATION 1.58 | -0.03 z-scores STANDARD_DEVIATION 1.14 | -0.18 z-scores STANDARD_DEVIATION 1.37 |
| Grooved Pegboard Non-dominant | -0.56 z-scores STANDARD_DEVIATION 1.82 | -0.48 z-scores STANDARD_DEVIATION 1.42 | -0.52 z-scores STANDARD_DEVIATION 1.61 |
| Region of Enrollment Uganda | 36 participants | 37 participants | 73 participants |
| Sex: Female, Male Female | 34 Participants | 32 Participants | 66 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 7 Participants |
| Symbol Digit | -0.87 z-scores STANDARD_DEVIATION 0.96 | -0.86 z-scores STANDARD_DEVIATION 0.8 | -0.86 z-scores STANDARD_DEVIATION 0.88 |
| WHO-UCLA Auditory Verbal Learning Test (AVLT): Delayed | -1.17 z-scores STANDARD_DEVIATION 0.79 | -1.15 z-scores STANDARD_DEVIATION 1.18 | -1.16 z-scores STANDARD_DEVIATION 1 |
| WHO-UCLA Auditory Verbal Learning Test (AVLT): Trials Total | -1.28 z-scores STANDARD_DEVIATION 0.88 | -1.48 z-scores STANDARD_DEVIATION 1.14 | -1.38 z-scores STANDARD_DEVIATION 1.02 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 26 / 36 | 25 / 37 |
| serious Total, serious adverse events | 2 / 36 | 1 / 37 |
Outcome results
Primary
24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum)
The U NP Sum is defined as the average of z scores for 9 neuropsychological test subcomponents in the neuropsychological test battery (i.e. the average of norm-adjusted (z) scores for Grooved Pegboard Dominant Hand, Grooved Pegboard Non-dominant Hand, Color Trails 1, Color Trails 2, Symbol Digit, WHO-UCLA Verbal Learning test Trial 5, WHO-UCLA Verbal Learning test delayed recall, Digit Span forward and Digit Span backward). The outcome is defined as U NP Sum at week 24 - U NP Sum at baseline.
Time frame: At baseline and week 24
Population: The descriptive statistics are based on per protocol analysis. For the statistical analysis, ITT analysis was used and the missing U NP Sums at week 24 were imputed using a multiple regression imputation method. The number of participants analyzed for the ITT analysis was 73 (36 for Minocycline and 37 for Placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | 24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) | 0.44 z-score | Standard Deviation 0.74 |
| Placebo | 24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) | 0.49 z-score | Standard Deviation 0.67 |
Comparison: The null hypothesis was that the 24-week changes of U NP Sum between the minocycline and placebo groups are the same.~The sample size calculation showed that 100 (50 participants in each group) were required to detect the clinically meaningful difference of 0.5 with 85% power, 0.05 Type I error, two-sample and two-sided test.p-value: 0.3795% CI: [-0.512, 0.46]Regression, Linear
Secondary
24-week Change of CD4 Cell Counts
The outcome is defined as CD4 cell count at week 24 - CD4 cell count at baseline. The unit is cells/mm\^3.
Time frame: At baseline and week 24
Population: This analysis used the participants with CD4 cell counts at baseline and week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | 24-week Change of CD4 Cell Counts | -25.28 cells/mm^3 | Standard Deviation 70.85 |
| Placebo | 24-week Change of CD4 Cell Counts | -28.57 cells/mm^3 | Standard Deviation 61.65 |
Comparison: The null hypothesis is that the mean 24-week change of CD4 cell counts in the minocycline group is the same as the one in the placebo group.p-value: 0.64795% CI: [-27.23, 43.45]Regression, Linear
Secondary
24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score
The outcome is the total CES-D score at week 24 - the total CES-D score at baseline. The total CES-D score is based on 20 CES-D items, such as I was bothered by things that usually don't bother me and I did not feel like eating, my appetite was poor. Patients were asked to answer each item by 4 scales: (1) Rarely, (2) Sometimes, (3) Occasionally, and (4) Most of the time. After 4 negative items were multiplied by -1, the total CES-D score is a simple sum of all items. The min and Max are 0 and 60, respectively. Higher scores indicate more severe depressive symptoms.
Time frame: At baseline and week 24
Population: The analysis includes participants with CES-D scores at baseline and week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | 24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score | -4.19 scores on a scale | Standard Deviation 10.86 |
| Placebo | 24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score | -4.04 scores on a scale | Standard Deviation 8.27 |
Comparison: The null hypothesis is that the mean 24-week change of CES-D score in the minocycline group is the same as the one in the placebo group.p-value: 0.91595% CI: [-3.4, 3.78]Regression, Linear
Secondary
24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed)
The outcome is the HIV RNA plasma viral loads (Log10 transformed) at week 24 - the viral loads (Log10 transformed) at baseline.
Time frame: At baseline and week 24
Population: The analysis includes participants with HIV RNA viral loads at baseline and week 24.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Minocycline | 24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed) | 0.22 copies/mL |
| Placebo | 24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed) | 0.13 copies/mL |
Comparison: The null hypothesis is that the median log10-transformed HIV RNA viral loads in the minocycline group is the same as the one in the placebo group.p-value: 0.766Kruskal-Wallis
Secondary
24-week Change of Instrumental Activities of Daily Living
The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline.
Time frame: At baseline and week 24
Population: The analysis includes participants with IADL scores at baseline and week 24.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Minocycline | 24-week Change of Instrumental Activities of Daily Living | Better | 14 percentage of participants |
| Minocycline | 24-week Change of Instrumental Activities of Daily Living | No Change/Worse | 86 percentage of participants |
| Placebo | 24-week Change of Instrumental Activities of Daily Living | Better | 12 percentage of participants |
| Placebo | 24-week Change of Instrumental Activities of Daily Living | No Change/Worse | 88 percentage of participants |
Comparison: The null hypothesis is that the percentage of being better at week 24 compared to baseline in the minocycline group is the same as the one in the placebo group.p-value: 0.76495% CI: [0.26, 6.34]Regression, Logistic
Secondary
24-week Change of Karnofsky Performance Score
The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline.
Time frame: At baseline and week 24
Population: This analysis includes the participants with Karnofsky performance score at baseline and week 24.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Minocycline | 24-week Change of Karnofsky Performance Score | No Change/Worse | 97 percentage of participants |
| Minocycline | 24-week Change of Karnofsky Performance Score | Better | 3 percentage of participants |
| Placebo | 24-week Change of Karnofsky Performance Score | No Change/Worse | 94 percentage of participants |
| Placebo | 24-week Change of Karnofsky Performance Score | Better | 6 percentage of participants |
Comparison: The null hypothesis is that the percentage of participants feeling better in the minocycline group after 24 week treatment is the same as the one in the placebo group.p-value: 0.61395% CI: [0.043, 0.062]Fisher Exact
Secondary
24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage
The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline.
Time frame: At baseline and week 24
Population: The descriptive statistics were based on observed data. Since all participants reported there were no change in the MSK score at week 24, no statistical test was conducted.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Minocycline | 24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage | No Change/Worse | 28 participants |
| Minocycline | 24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage | Better | 0 participants |
| Placebo | 24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage | No Change/Worse | 27 participants |
| Placebo | 24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage | Better | 0 participants |
Secondary
48-week Change of CD4 Cell Counts
The outcome is defined as CD4 cell count at week 48 - CD4 cell count at baseline. The unit is cells/mm\^3.
Time frame: At baseline and week 48
Population: This analysis used the participants with CD4 cell counts at baseline and week 48.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | 48-week Change of CD4 Cell Counts | -61.15 cells/mm^3 | Standard Deviation 80.46 |
| Placebo | 48-week Change of CD4 Cell Counts | -56.50 cells/mm^3 | Standard Deviation 84.97 |
Comparison: The null hypothesis is that the mean 48-week change in CD4 cell counts in the minocycline group is the same as the one in the placebo group.p-value: 0.81395% CI: [-59.07, 74.6]Regression, Linear
Secondary
Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms
The outcome is the time of first Grade ≥ 2 toxicity and/or sign and symptoms from treatment initiation up to 48 weeks. The grade was determined by clinicians and an Grade ≥ 2 event means moderate, severe, life-threatening, or death event.
Time frame: Time of first Grade ≥ 2 toxicity and/or sign and symptom event up to 48 weeks
Population: This analysis includes every randomized participants. A total of 22 minocycline and 21 placebo participants reported at least one Grade ≥ 2 toxicity and/or sign and symptoms during 48 weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Minocycline | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms | 0-4 weeks | 12 participants with an event |
| Minocycline | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms | 4.01-12 weeks | 6 participants with an event |
| Minocycline | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms | 12.01-24 weeks | 3 participants with an event |
| Minocycline | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms | 24.01-48 weeks | 1 participants with an event |
| Placebo | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms | 24.01-48 weeks | 1 participants with an event |
| Placebo | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms | 0-4 weeks | 10 participants with an event |
| Placebo | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms | 12.01-24 weeks | 3 participants with an event |
| Placebo | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms | 4.01-12 weeks | 7 participants with an event |
Comparison: The null hypothesis is that the 48-week survival curve for the first Grade ≥ 2 toxicity and/or sign and symptoms in the minocycline group is the same as the one in the placebo group.p-value: 0.941Log Rank
Secondary
Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms.
The outcome is the time to first Grade ≥ 2 toxicity and/or sign and symptoms from study treatment initiation up to week 24. The grade was determined by clinicians and an Grade ≥ 2 event means moderate, severe, life-threatening, or death event.
Time frame: Time of initial Grade ≥ 2 toxicity and/or sign and symptom event up to week 24
Population: This analysis includes every randomized participants. A total of 21 minocycline and 20 placebo participants reported at least one Grade ≥ 2 toxicity and/or sign and symptoms during 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Minocycline | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. | 12.01 - 24 weeks | 3 participants with an event |
| Minocycline | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. | 0-4 weeks | 12 participants with an event |
| Minocycline | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. | 4.01 - 12 weeks | 6 participants with an event |
| Placebo | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. | 4.01 - 12 weeks | 7 participants with an event |
| Placebo | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. | 0-4 weeks | 10 participants with an event |
| Placebo | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. | 12.01 - 24 weeks | 3 participants with an event |
Comparison: The null hypothesis is that the survival curve for the first Grade ≥ 2 toxicity and/or sign and symptoms in the minocycline group is the same as the one in the placebo group.p-value: 0.661Log Rank