Cocaine Abuse, Cocaine Dependence
Conditions
Keywords
cocaine abuse, cocaine dependence, postpartum period
Brief summary
The investigators propose a placebo-controlled, randomized clinical trial that would enroll 50 postpartum women with a history of cocaine abuse or dependence to assess whether progesterone (100mgs twice daily) decreases postpartum cocaine use.
Detailed description
Specific Aim 1: To evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Hypothesis 1: Compared to women who are randomized to placebo, those assigned to progesterone will use less cocaine as measured by urine toxicology results and self-reported days of use. Specific aim 2: To obtain information about the safety and tolerability of progesterone treatment in the postpartum period. Hypothesis 2: Side effects for progesterone will be similar to those of placebo.
Interventions
DRUGProgesterone
100mgs progesterone twice daily
OTHERPlacebo
Matched placebo pills to be taken twice daily
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Gravidas (women who delivered a baby in the past 12 weeks) who are 18 or older are eligible to participate. * Women must meet diagnostic criteria for abuse or dependence of cocaine in the six-months prior to conception or during pregnancy. * Women who abuse other illicit substances or alcohol would also be eligible as long as cocaine was their primary drug of abuse. If women are also opiate dependent, they must be undergoing treatment with methadone or buprenorphine. While we propose to target cocaine we will also monitor the ability of women with polysubstance use to maintain abstinence from substances other than cocaine.
Exclusion criteria
Women will be ineligible for the trial if they: 1. have a history of major medical illnesses including liver diseases, suspected or known malignancy, thrombophlebitis, deep vein thrombosis, pulmonary embolus, clotting or bleeding disorders, heart disease, diabetes, history of stroke or other medical conditions that the physician investigator deems as contraindicated for participation in the study; 2. have a known allergy to progesterone or peanuts (vehicle for micronized progesterone); 3. speak a language other than English; 4. are planning on moving out of the area in the first six months after delivery; 5. are unable to understand the study or are unable to provide informed consent; 6. are currently undergoing treatment with another pharmacological agent for substance abuse treatment (with the exception of methadone or buprenorphine as above); 7. have pending incarceration; 8. are currently incarcerated; 9. are using another progestin; 10. are unwilling to accept randomization; 11. are unwilling to use a barrier method of birth control for the duration of the study to ensure that they will not become pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Number of Days Per Week of Cocaine Use | Weekly measurements, Baseline to 12 weeks | Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Measured by self-reported days of cocaine use per week via substance use calendar. |
| Number of Days of Cocaine Use Between 12 Week Visits & the 3 Month Follow up | baseline, end of trial (week 12), 3-month post-trial follow-up | Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Measured by self-reported days of cocaine use per week during the trial period and during 3 month follow up using the substance use calendar |
| Proportion of Positive Urine Samples Per Week | weekly measurements, baseline to 12 weeks | Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Urine tox tests obtained qualitative and quantitative data on cocaine metabolites and other substances. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Comparison of Adverse Events Between Women in Placebo and Progesterone Group | 12 weeks postpartum | To obtain information about the safety and tolerability of progesterone treatment in the postpartum period, women were queried at every visit about onset of adverse events, their seriousness, and their relatedness to study medication. Such data was monitored in SAETRS. |
| Salivary Progesterone Concentrations | week 2, week 6, week 10, week 12 | A comparison of salivary progesterone concentrations across all samples for all timepoints |
| Cocaine Craving (Measured Weekly Using CCQ-Brief) | baseline to 12 weeks | CCQ-Brief is a ten-item questionnaire developed from the 45-item CCQ. Each item is scored on a visual analogue scale ranging from 1-7, and items are averaged to yield a score from 1 to 7. Higher scores indicate stronger cocaine cravings. |
| Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | baseline to 12 weeks | EPDS scores were measured to detect depression as a possible adverse event and compare scores between the two groups. The scale consists of 10 items. Each item is scored from 0 to 3, and the 10 items are summed to calculate a total score with a possible range of 0 to 30 and higher scores indicating more severe depression. |
Countries
United States
Participant flow
Recruitment details
On-site clinic screening assessments were performed in three obstetrics clinic associated with the Yale New Haven Hospital System in New Haven, CT, USA. Study referrals were accepted from the New Haven area. Both post-partum and pregnant women were screened. Screenings began in October of 2010 and finished in February of 2013.
Pre-assignment details
75 women were scheduled for intake, but 24 did not complete intake interview and 1 was ineligible for randomisation because of a medical issue. The first 50 eligible women were randomly assigned.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matched placebo pills to be taken twice daily
Placebo: Matched placebo pills to be taken twice daily | 25 |
| Progesterone 100 mgs progesterone twice daily
Progesterone: 100mgs progesterone twice daily | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 4 |
| Overall Study | Received inpatient substance treatment | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Placebo | Progesterone |
|---|---|---|---|
| Age at first cocaine use (years) | 19.9 years STANDARD_DEVIATION 2.2 | 20.6 years STANDARD_DEVIATION 6.3 | 19.2 years STANDARD_DEVIATION 4 |
| Age, Continuous | 31.6 years STANDARD_DEVIATION 2.4 | 32.6 years STANDARD_DEVIATION 6.3 | 30.5 years STANDARD_DEVIATION 4.5 |
| Any lifetime major depressive episode History of MDD | 7 participants | 4 participants | 3 participants |
| Any lifetime major depressive episode No history of MDD | 43 participants | 21 participants | 22 participants |
| Baseline cocaine use (days per week) | 1.1 days STANDARD_DEVIATION 1 | 0.41 days STANDARD_DEVIATION 0.91 | 1.15 days STANDARD_DEVIATION 3.84 |
| Education High school | 17 participants | 8 participants | 9 participants |
| Education Less than high shool | 13 participants | 9 participants | 4 participants |
| Education Post-high school | 20 participants | 8 participants | 12 participants |
| Employment status In paid employment | 10 participants | 7 participants | 3 participants |
| Employment status Not in paid employment | 37 participants | 17 participants | 20 participants |
| Employment status Unknown | 3 participants | 1 participants | 2 participants |
| EPDS score at intake | 11.2 units on a scale STANDARD_DEVIATION 3.9 | 11.2 units on a scale STANDARD_DEVIATION 6.7 | 11.2 units on a scale STANDARD_DEVIATION 7.2 |
| Generalized anxiety disorder no | 36 participants | 19 participants | 17 participants |
| Generalized anxiety disorder yes | 14 participants | 6 participants | 8 participants |
| Lifetime cocaine use (years) | 7.4 years STANDARD_DEVIATION 2.8 | 8.5 years STANDARD_DEVIATION 7.2 | 6.2 years STANDARD_DEVIATION 4.2 |
| Marital status Dating | 7 participants | 6 participants | 1 participants |
| Marital status Divorced | 4 participants | 3 participants | 1 participants |
| Marital status Married or cohabitating | 12 participants | 5 participants | 7 participants |
| Marital status Separated | 4 participants | 2 participants | 2 participants |
| Marital status Single | 23 participants | 9 participants | 14 participants |
| Methadone maintained not using methadone | 28 participants | 17 participants | 11 participants |
| Methadone maintained Using methadone | 22 participants | 8 participants | 14 participants |
| Not using cocaine at intake Not using cocaine at intake | 41 participants | 22 participants | 19 participants |
| Not using cocaine at intake Using cocaine at intake | 9 participants | 3 participants | 6 participants |
| Obsessive compulsive disorder no | 46 participants | 21 participants | 25 participants |
| Obsessive compulsive disorder yes | 4 participants | 4 participants | 0 participants |
| Parity | 2.4 births STANDARD_DEVIATION 0.2 | 2.6 births STANDARD_DEVIATION 1.6 | 2.1 births STANDARD_DEVIATION 1.4 |
| Post-traumatic stress disorder no | 39 participants | 20 participants | 19 participants |
| Post-traumatic stress disorder yes | 11 participants | 5 participants | 6 participants |
| Race/Ethnicity, Customized Black | 16 participants | 12 participants | 4 participants |
| Race/Ethnicity, Customized Hispanic or other | 6 participants | 1 participants | 5 participants |
| Race/Ethnicity, Customized White | 28 participants | 12 participants | 16 participants |
| Region of Enrollment United States | 50 participants | 25 participants | 25 participants |
| Sex: Female, Male Female | 50 Participants | 25 Participants | 25 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Social phobia History of social phobia | 6 participants | 5 participants | 1 participants |
| Social phobia No history of social phobia | 44 participants | 20 participants | 24 participants |
| Weeks post partum | 3.5 weeks STANDARD_DEVIATION 2.3 | 3.4 weeks STANDARD_DEVIATION 5.1 | 3.6 weeks STANDARD_DEVIATION 4.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 25 | 15 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Mean Number of Days Per Week of Cocaine Use
Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Measured by self-reported days of cocaine use per week via substance use calendar.
Time frame: Weekly measurements, Baseline to 12 weeks
Population: intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Number of Days Per Week of Cocaine Use | Week 2 | 0.45 number of days per week of cocaine use | Standard Deviation 0.89 |
| Placebo | Mean Number of Days Per Week of Cocaine Use | Week 7 | 0.56 number of days per week of cocaine use | Standard Deviation 1.3 |
| Placebo | Mean Number of Days Per Week of Cocaine Use | Week 4 | 0.49 number of days per week of cocaine use | Standard Deviation 0.94 |
| Placebo | Mean Number of Days Per Week of Cocaine Use | Week 8 | 0.59 number of days per week of cocaine use | Standard Deviation 1.37 |
| Placebo | Mean Number of Days Per Week of Cocaine Use | Week 1 | 0.43 number of days per week of cocaine use | Standard Deviation 0.88 |
| Placebo | Mean Number of Days Per Week of Cocaine Use | Week 9 | 0.62 number of days per week of cocaine use | Standard Deviation 1.55 |
| Placebo | Mean Number of Days Per Week of Cocaine Use | Week 5 | 0.52 number of days per week of cocaine use | Standard Deviation 1.02 |
| Placebo | Mean Number of Days Per Week of Cocaine Use | Week 10 | 0.64 number of days per week of cocaine use | Standard Deviation 1.68 |
| Placebo | Mean Number of Days Per Week of Cocaine Use | Week 3 | 0.47 number of days per week of cocaine use | Standard Deviation 0.91 |
| Placebo | Mean Number of Days Per Week of Cocaine Use | Week 11 | 0.67 number of days per week of cocaine use | Standard Deviation 1.91 |
| Placebo | Mean Number of Days Per Week of Cocaine Use | Week 6 | 0.52 number of days per week of cocaine use | Standard Deviation 1.13 |
| Placebo | Mean Number of Days Per Week of Cocaine Use | Week 12 | 0.70 number of days per week of cocaine use | Standard Deviation 2.11 |
| Placebo | Mean Number of Days Per Week of Cocaine Use | Baseline | 0.41 number of days per week of cocaine use | Standard Deviation 0.91 |
| Progesterone | Mean Number of Days Per Week of Cocaine Use | Week 12 | 0.24 number of days per week of cocaine use | Standard Deviation 0.68 |
| Progesterone | Mean Number of Days Per Week of Cocaine Use | Baseline | 1.15 number of days per week of cocaine use | Standard Deviation 3.84 |
| Progesterone | Mean Number of Days Per Week of Cocaine Use | Week 1 | 1.01 number of days per week of cocaine use | Standard Deviation 3.15 |
| Progesterone | Mean Number of Days Per Week of Cocaine Use | Week 2 | 0.89 number of days per week of cocaine use | Standard Deviation 2.51 |
| Progesterone | Mean Number of Days Per Week of Cocaine Use | Week 3 | 0.78 number of days per week of cocaine use | Standard Deviation 2.16 |
| Progesterone | Mean Number of Days Per Week of Cocaine Use | Week 4 | 0.68 number of days per week of cocaine use | Standard Deviation 1.87 |
| Progesterone | Mean Number of Days Per Week of Cocaine Use | Week 5 | 0.60 number of days per week of cocaine use | Standard Deviation 1.62 |
| Progesterone | Mean Number of Days Per Week of Cocaine Use | Week 6 | 0.53 number of days per week of cocaine use | Standard Deviation 1.41 |
| Progesterone | Mean Number of Days Per Week of Cocaine Use | Week 7 | 0.46 number of days per week of cocaine use | Standard Deviation 1.18 |
| Progesterone | Mean Number of Days Per Week of Cocaine Use | Week 8 | 0.41 number of days per week of cocaine use | Standard Deviation 1.04 |
| Progesterone | Mean Number of Days Per Week of Cocaine Use | Week 9 | 0.36 number of days per week of cocaine use | Standard Deviation 0.92 |
| Progesterone | Mean Number of Days Per Week of Cocaine Use | Week 10 | 0.31 number of days per week of cocaine use | Standard Deviation 0.89 |
| Progesterone | Mean Number of Days Per Week of Cocaine Use | Week 11 | 0.28 number of days per week of cocaine use | Standard Deviation 0.76 |
p-value: 0.0195% CI: [1.04, 1.36]Generalized Estimating Equation
Primary
Number of Days of Cocaine Use Between 12 Week Visits & the 3 Month Follow up
Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Measured by self-reported days of cocaine use per week during the trial period and during 3 month follow up using the substance use calendar
Time frame: baseline, end of trial (week 12), 3-month post-trial follow-up
Population: intent-to-treat
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Number of Days of Cocaine Use Between 12 Week Visits & the 3 Month Follow up | Baseline | 0.5200 days of cocaine use between visits |
| Placebo | Number of Days of Cocaine Use Between 12 Week Visits & the 3 Month Follow up | End of Trial (Week 12) | 0.2860 days of cocaine use between visits |
| Placebo | Number of Days of Cocaine Use Between 12 Week Visits & the 3 Month Follow up | 3-Month Post-Trial Follow-Up | 12.8472 days of cocaine use between visits |
| Progesterone | Number of Days of Cocaine Use Between 12 Week Visits & the 3 Month Follow up | Baseline | 1.6800 days of cocaine use between visits |
| Progesterone | Number of Days of Cocaine Use Between 12 Week Visits & the 3 Month Follow up | End of Trial (Week 12) | 0.05550 days of cocaine use between visits |
| Progesterone | Number of Days of Cocaine Use Between 12 Week Visits & the 3 Month Follow up | 3-Month Post-Trial Follow-Up | 1.3659 days of cocaine use between visits |
Comparison: We calculated that a sample size of 50 women would have 80% power to detect a significant (p\<0.05) difference between groups if the effect size for the primary outcome was large.p-value: 0.00395% CI: [3.18, 290.04]Generalized Estimating Equation
Comparison: Negative binomial distribution, log link, and first-order autoregressive covariance structurep-value: 0.03895% CI: [1.18, 235.52]Generalized Estimating Equation
Primary
Proportion of Positive Urine Samples Per Week
Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Urine tox tests obtained qualitative and quantitative data on cocaine metabolites and other substances.
Time frame: baseline, end of trial (week 12) and 3-month post-trial follow-up
Population: intent-to-treat
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Proportion of Positive Urine Samples Per Week | Baseline | 0.2400 proportion of positive urines per week |
| Placebo | Proportion of Positive Urine Samples Per Week | Week 12 | 0.3173 proportion of positive urines per week |
| Placebo | Proportion of Positive Urine Samples Per Week | 3 month post-trial follow-up | 0.3952 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Baseline | 0.1582 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Week 12 | 0.1904 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | 3 month post-trial follow-up | 0.2246 proportion of positive urines per week |
Comparison: We calculated that a sample size of 50 women would have 80% power to detect a significant (p\<0.05) difference between groups if the effect size for the primary outcome was large.p-value: 0.7595% CI: [0.23, 7.88]Generalized Estimating Equation
p-value: 0.8495% CI: [0.24, 5.84]Generalized Estimating Equation
Primary
Proportion of Positive Urine Samples Per Week
Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Urine tox tests obtained qualitative and quantitative data on cocaine metabolites and other substances.
Time frame: weekly measurements, baseline to 12 weeks
Population: intent-to-treat
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Proportion of Positive Urine Samples Per Week | Week 12 | 0.2918 proportion of positive urines per week |
| Placebo | Proportion of Positive Urine Samples Per Week | Week 5 | 0.2757 proportion of positive urines per week |
| Placebo | Proportion of Positive Urine Samples Per Week | Week 2 | 0.2689 proportion of positive urines per week |
| Placebo | Proportion of Positive Urine Samples Per Week | Week 6 | 0.2780 proportion of positive urines per week |
| Placebo | Proportion of Positive Urine Samples Per Week | Week 11 | 0.2895 proportion of positive urines per week |
| Placebo | Proportion of Positive Urine Samples Per Week | Week 7 | 0.2803 proportion of positive urines per week |
| Placebo | Proportion of Positive Urine Samples Per Week | Week 3 | 0.2712 proportion of positive urines per week |
| Placebo | Proportion of Positive Urine Samples Per Week | Week 8 | 0.2826 proportion of positive urines per week |
| Placebo | Proportion of Positive Urine Samples Per Week | Baseline | 0.2645 proportion of positive urines per week |
| Placebo | Proportion of Positive Urine Samples Per Week | Week 9 | 0.2849 proportion of positive urines per week |
| Placebo | Proportion of Positive Urine Samples Per Week | Week 4 | 0.2734 proportion of positive urines per week |
| Placebo | Proportion of Positive Urine Samples Per Week | Week 10 | 0.2872 proportion of positive urines per week |
| Placebo | Proportion of Positive Urine Samples Per Week | Week 1 | 0.2667 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Week 10 | 0.2154 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Week 1 | 0.2006 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Week 11 | 0.2171 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Week 12 | 0.2189 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Baseline | 0.1990 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Week 2 | 0.2022 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Week 3 | 0.2038 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Week 4 | 0.2054 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Week 5 | 0.2071 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Week 6 | 0.2087 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Week 7 | 0.2104 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Week 8 | 0.2121 proportion of positive urines per week |
| Progesterone | Proportion of Positive Urine Samples Per Week | Week 9 | 0.2138 proportion of positive urines per week |
Comparison: We calculated that a sample size of 50 women would have 80% power to detect a significant (p\<0.05) difference between groups if the effect size for the primary outcome was large.p-value: 0.9995% CI: [0.87, 1.15]Generalized Estimating Equation
Secondary
Cocaine Craving (Measured Weekly Using CCQ-Brief)
CCQ-Brief is a ten-item questionnaire developed from the 45-item CCQ. Each item is scored on a visual analogue scale ranging from 1-7, and items are averaged to yield a score from 1 to 7. Higher scores indicate stronger cocaine cravings.
Time frame: baseline to 12 weeks
Population: intent-to-treat
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 2 | 1.5285 units on a scale |
| Placebo | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 7 | 1.4454 units on a scale |
| Placebo | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 4 | 1.4947 units on a scale |
| Placebo | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 8 | 1.4293 units on a scale |
| Placebo | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 1 | 1.5456 units on a scale |
| Placebo | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 9 | 1.4134 units on a scale |
| Placebo | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 5 | 1.4781 units on a scale |
| Placebo | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 10 | 1.3977 units on a scale |
| Placebo | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 3 | 1.5115 units on a scale |
| Placebo | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 11 | 1.3822 units on a scale |
| Placebo | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 6 | 1.4616 units on a scale |
| Placebo | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 12 | 1.3668 units on a scale |
| Placebo | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Baseline | 1.5630 units on a scale |
| Progesterone | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 12 | 1.4300 units on a scale |
| Progesterone | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Baseline | 1.6752 units on a scale |
| Progesterone | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 1 | 1.6532 units on a scale |
| Progesterone | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 2 | 1.6316 units on a scale |
| Progesterone | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 3 | 1.6102 units on a scale |
| Progesterone | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 4 | 1.5891 units on a scale |
| Progesterone | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 5 | 1.5683 units on a scale |
| Progesterone | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 6 | 1.5478 units on a scale |
| Progesterone | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 7 | 1.5275 units on a scale |
| Progesterone | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 8 | 1.5075 units on a scale |
| Progesterone | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 9 | 1.4877 units on a scale |
| Progesterone | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 10 | 1.4682 units on a scale |
| Progesterone | Cocaine Craving (Measured Weekly Using CCQ-Brief) | Week 11 | 1.4490 units on a scale |
p-value: 0.9116Generalized Estimating Equation
Secondary
Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS))
EPDS scores were measured to detect depression as a possible adverse event and compare scores between the two groups. The scale consists of 10 items. Each item is scored from 0 to 3, and the 10 items are summed to calculate a total score with a possible range of 0 to 30 and higher scores indicating more severe depression.
Time frame: baseline to 12 weeks
Population: intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 3 | 6.91 units on a scale | Standard Error 1.04 |
| Placebo | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 7 | 9.13 units on a scale | Standard Error 1.71 |
| Placebo | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Baseline | 10.84 units on a scale | Standard Error 1.37 |
| Placebo | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 8 | 8.29 units on a scale | Standard Error 1.64 |
| Placebo | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 4 | 9.27 units on a scale | Standard Error 1.6 |
| Placebo | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 9 | 8.24 units on a scale | Standard Error 1.7 |
| Placebo | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 2 | 8.57 units on a scale | Standard Error 1.19 |
| Placebo | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 10 | 8.55 units on a scale | Standard Error 1.69 |
| Placebo | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 5 | 7.60 units on a scale | Standard Error 1.54 |
| Placebo | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 1 | 8.05 units on a scale | Standard Error 1.37 |
| Placebo | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 12 | 8.38 units on a scale | Standard Error 1.71 |
| Placebo | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 6 | 8.05 units on a scale | Standard Error 1.52 |
| Placebo | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | 3-month post trial | 9.09 units on a scale | Standard Error 1.43 |
| Placebo | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 11 | 7.33 units on a scale | Standard Error 1.43 |
| Progesterone | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | 3-month post trial | 7.21 units on a scale | Standard Error 1.32 |
| Progesterone | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Baseline | 11.08 units on a scale | Standard Error 1.44 |
| Progesterone | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 1 | 8.61 units on a scale | Standard Error 1.41 |
| Progesterone | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 2 | 6.65 units on a scale | Standard Error 1.03 |
| Progesterone | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 3 | 6.95 units on a scale | Standard Error 1.41 |
| Progesterone | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 4 | 6.62 units on a scale | Standard Error 1.08 |
| Progesterone | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 5 | 6.62 units on a scale | Standard Error 1.09 |
| Progesterone | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 6 | 7.24 units on a scale | Standard Error 1.48 |
| Progesterone | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 7 | 6.53 units on a scale | Standard Error 1.41 |
| Progesterone | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 8 | 6.16 units on a scale | Standard Error 1.48 |
| Progesterone | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 9 | 6.68 units on a scale | Standard Error 1.77 |
| Progesterone | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 10 | 6.64 units on a scale | Standard Error 1.33 |
| Progesterone | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 11 | 6.85 units on a scale | Standard Error 1.4 |
| Progesterone | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | Week 12 | 6.60 units on a scale | Standard Error 1.15 |
Secondary
Overall Comparison of Adverse Events Between Women in Placebo and Progesterone Group
To obtain information about the safety and tolerability of progesterone treatment in the postpartum period, women were queried at every visit about onset of adverse events, their seriousness, and their relatedness to study medication. Such data was monitored in SAETRS.
Time frame: 12 weeks postpartum
Population: intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Overall Comparison of Adverse Events Between Women in Placebo and Progesterone Group | 11 adverse events |
| Progesterone | Overall Comparison of Adverse Events Between Women in Placebo and Progesterone Group | 15 adverse events |
p-value: 0.103Fisher Exact
Secondary
Salivary Progesterone Concentrations
A comparison of salivary progesterone concentrations across all samples for all timepoints
Time frame: week 2, week 6, week 10, week 12
Population: intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Salivary Progesterone Concentrations | Week 2 | 165.94 pg/ml of salivary progesterone | Standard Error 135.3 |
| Placebo | Salivary Progesterone Concentrations | Week 6 | 189.38 pg/ml of salivary progesterone | Standard Error 237.94 |
| Placebo | Salivary Progesterone Concentrations | Week 10 | 124.30 pg/ml of salivary progesterone | Standard Error 72.31 |
| Placebo | Salivary Progesterone Concentrations | Week 12 | 235.04 pg/ml of salivary progesterone | Standard Error 288.51 |
| Progesterone | Salivary Progesterone Concentrations | Week 12 | 866.10 pg/ml of salivary progesterone | Standard Error 1044.84 |
| Progesterone | Salivary Progesterone Concentrations | Week 2 | 797.26 pg/ml of salivary progesterone | Standard Error 1004.13 |
| Progesterone | Salivary Progesterone Concentrations | Week 10 | 1771.07 pg/ml of salivary progesterone | Standard Error 3139.36 |
| Progesterone | Salivary Progesterone Concentrations | Week 6 | 1580.95 pg/ml of salivary progesterone | Standard Error 1963.51 |
Post Hoc
Relapse to Cocaine Use During Treatment Period
Post-hoc sensitivity test to compare hazard of relapse to cocaine use between two treatment groups among participants (n=41) who did not report using cocaine at intake.
Time frame: baseline to 12 weeks
Population: intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Relapse to Cocaine Use During Treatment Period | 9 participants who relapsed to cocaine use |
| Progesterone | Relapse to Cocaine Use During Treatment Period | 3 participants who relapsed to cocaine use |
p-value: 0.04895% CI: [1.09, 20.5]Regression, Cox
Post Hoc
Relapse to Cocaine Use During Treatment Period or 3 Months Post Treatment
Post-hoc sensitivity test to compare hazard of relapse to cocaine use between two treatment groups among participants (n=41) who did not report using cocaine at intake.
Time frame: baseline to 3 months post 12-week trial period
Population: intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Relapse to Cocaine Use During Treatment Period or 3 Months Post Treatment | 10 participants who relapsed to cocaine use |
| Progesterone | Relapse to Cocaine Use During Treatment Period or 3 Months Post Treatment | 4 participants who relapsed to cocaine use |
p-value: 0.0695% CI: [0.92, 13.3]Regression, Cox