Trial Outcomes & Findings for Ketamine to Improve Recovery After Cesarean Delivery - Part 1 (NCT NCT04037085)

NCT ID: NCT04037085

Last Updated: 2022-12-20

Results Overview

Plasma will be used to calculate area under the plasma concentration-time curve (AUC 0-∞) of ketamine levels during infusion. The area under the plasma drug concentration-time curve (AUC) reflects the actual body exposure to drug after administration of a dose of the drug.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 8 participants
• Primary outcome timeframe: 12 hour ketamine infusion
• Results posted on: 2022-12-20

Participant Flow

Participant milestones

Measure	Ketamine Ketamine - IV after cord clamping; IV infusion for 12 hours OR in the weaning population IV Ketamine infusion for 12 hours in the Montefiore CTRC Ketamine: Subjects in the intervention arm will receive bolus and infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation. For the weaning population, they will receive a 12 hour infusion in the CTRC and stay an additional 12 hours in the CTRC (or until discharged). Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and for 12 hours after infusion discontinuation.
Overall Study STARTED	8
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ketamine to Improve Recovery After Cesarean Delivery - Part 1

Baseline characteristics by cohort

Measure	Ketamine n=8 Participants Ketamine - IV after cord clamping; IV infusion for 12 hours OR in the weaning population IV Ketamine infusion for 12 hours in the Montefiore CTRC Ketamine: Subjects in the intervention arm will receive bolus and infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation. For the weaning population, they will receive a 12 hour infusion in the CTRC and stay an additional 12 hours in the CTRC (or until discharged). Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and for 12 hours after infusion discontinuation.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Age, Continuous	36.1 years STANDARD_DEVIATION 3.31 • n=93 Participants
Sex: Female, Male Female	8 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants
Race (NIH/OMB) White	6 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	8 participants n=93 Participants
Number of pregnancies	2 pregnancies n=93 Participants
Parity	2 live births n=93 Participants
Maternal Weight	90.613 Kilograms (kg) n=93 Participants

PRIMARY outcome

Timeframe: 12 hour ketamine infusion

Plasma will be used to calculate area under the plasma concentration-time curve (AUC 0-∞) of ketamine levels during infusion. The area under the plasma drug concentration-time curve (AUC) reflects the actual body exposure to drug after administration of a dose of the drug.

Outcome measures

Measure

Ketamine n=8 Participants Ketamine - IV after cord clamping; IV infusion for 12 hours OR in the weaning population IV Ketamine infusion for 12 hours in the Montefiore CTRC Ketamine: Subjects in the intervention arm will receive bolus and infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation. For the weaning population, they will receive a 12 hour infusion in the CTRC and stay an additional 12 hours in the CTRC (or until discharged). Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and for 12 hours after infusion discontinuation.

Ketamine (AUC)

28.46 mcg*min/mL Standard Deviation 9.97

PRIMARY outcome

Timeframe: 12 hours after ketamine infusion start

Ketamine steady state (Css) is defined as the concentration of drug in plasma at steady state.

Outcome measures

Measure

Ketamine n=8 Participants Ketamine - IV after cord clamping; IV infusion for 12 hours OR in the weaning population IV Ketamine infusion for 12 hours in the Montefiore CTRC Ketamine: Subjects in the intervention arm will receive bolus and infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation. For the weaning population, they will receive a 12 hour infusion in the CTRC and stay an additional 12 hours in the CTRC (or until discharged). Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and for 12 hours after infusion discontinuation.

Steady State (Css)

35.58 ng/mL

PRIMARY outcome

Timeframe: 27 hours postpartum or 24 hour CTRC appointment for weaning population

Postpartum maternal plasma serum will be used to calculate postpartum maternal ketamine half-life (T1/2). b. Elimination half-life (t½) is the time required for drug concentration to decrease by one-half at the end drug dosing. Elimination half-life was obtained from the slope of terminal elimination phase.

Outcome measures

Measure

Ketamine n=8 Participants Ketamine - IV after cord clamping; IV infusion for 12 hours OR in the weaning population IV Ketamine infusion for 12 hours in the Montefiore CTRC Ketamine: Subjects in the intervention arm will receive bolus and infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation. For the weaning population, they will receive a 12 hour infusion in the CTRC and stay an additional 12 hours in the CTRC (or until discharged). Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and for 12 hours after infusion discontinuation.

Elimination Half Life (T1/2) for Ketamine

364 Minutes Standard Deviation 121

PRIMARY outcome

Timeframe: 27 hours postpartum or 24 hour CTRC appointment for weaning population

Volume Distribution Steady State (Vdss) is the period of dynamic equilibrium of the drug calculated as the amount of drug in the body at time, t divided by the plasma concentration of the drug at time, t.

Outcome measures

Measure

Ketamine n=8 Participants Ketamine - IV after cord clamping; IV infusion for 12 hours OR in the weaning population IV Ketamine infusion for 12 hours in the Montefiore CTRC Ketamine: Subjects in the intervention arm will receive bolus and infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation. For the weaning population, they will receive a 12 hour infusion in the CTRC and stay an additional 12 hours in the CTRC (or until discharged). Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and for 12 hours after infusion discontinuation.

Volume of Distribution Steady State (Vdss)

1076 Liters Standard Deviation 617

PRIMARY outcome

Timeframe: 27 hours postpartum or 24 hour CTRC appointment for weaning population

Milk to plasma ratio for KET were calculated by dividing the concentration of the respective components Ketamine in human milk by plasma concentration at the corresponding times (± 30 min). Ratios higher than 1 indicate breastmilk concentrations of ketamine and the metabolites would be higher in breastmilk than in maternal plasma concentrations.

Outcome measures

Measure

Ketamine n=8 Participants Ketamine - IV after cord clamping; IV infusion for 12 hours OR in the weaning population IV Ketamine infusion for 12 hours in the Montefiore CTRC Ketamine: Subjects in the intervention arm will receive bolus and infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation. For the weaning population, they will receive a 12 hour infusion in the CTRC and stay an additional 12 hours in the CTRC (or until discharged). Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and for 12 hours after infusion discontinuation.

Ketamine Milk to Plasma Ratio (M:P)

3.15 Ratio Standard Deviation 1.05

PRIMARY outcome

Timeframe: 27 hours postpartum or 24 hour CTRC appointment for weaning population

Milk to plasma ratio of the Ketamine metabolite, Norketamine, calculated as the percentage of the maternal ketamine dose found from breastmilk. Milk to plasma ratio for NKET was calculated by dividing the concentration of the respective components Ketamine and Ketamine metabolites in human milk by plasma concentration at the corresponding times (± 30 min). Ratios higher than 1 indicate breastmilk concentrations of metabolites would be higher in breastmilk than in maternal plasma concentrations.

Outcome measures

Measure

Ketamine n=8 Participants Ketamine - IV after cord clamping; IV infusion for 12 hours OR in the weaning population IV Ketamine infusion for 12 hours in the Montefiore CTRC Ketamine: Subjects in the intervention arm will receive bolus and infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation. For the weaning population, they will receive a 12 hour infusion in the CTRC and stay an additional 12 hours in the CTRC (or until discharged). Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and for 12 hours after infusion discontinuation.

Nor-ketamine Milk to Plasma Ratio

1.5 Ratio Standard Deviation 0.19

PRIMARY outcome

Timeframe: 27 hours postpartum or 24 hour CTRC appointment for weaning population

Milk to plasma ratio of the Ketamine metabolite, Hydroxynorketamine, calculated as the percentage of the maternal ketamine dose found from breastmilk. Milk to plasma ratio for hydroxynorketamine was calculated by dividing the concentration of the respective ketamine metabolites in human milk by plasma concentration at the corresponding times (± 30 min). Ratios higher than 1 indicate breastmilk concentrations of the metabolites would be higher in breastmilk than in maternal plasma concentrations.

Outcome measures

Measure

Ketamine n=8 Participants Ketamine - IV after cord clamping; IV infusion for 12 hours OR in the weaning population IV Ketamine infusion for 12 hours in the Montefiore CTRC Ketamine: Subjects in the intervention arm will receive bolus and infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation. For the weaning population, they will receive a 12 hour infusion in the CTRC and stay an additional 12 hours in the CTRC (or until discharged). Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and for 12 hours after infusion discontinuation.

Hydroxynorketamine M:P Ratio

0.06 Ratio Standard Deviation 0.015

PRIMARY outcome

Timeframe: 27 hours postpartum or 24 hour CTRC appointment for weaning population

Relative infant dose will be calculated as the percentage of the maternal ketamine dose found from breastmilk. The relative infant dose was calculated from the concentrations of ketamine in breast milk at different times following ketamine administration to the women. The concentration of ketamine was converted to amount by multiplying with the volume of breast milk collected at various time intervals. The cumulative dose of ketamine was calculated. An RID ≤10% was considered low.

Outcome measures

Measure

Ketamine n=8 Participants Ketamine - IV after cord clamping; IV infusion for 12 hours OR in the weaning population IV Ketamine infusion for 12 hours in the Montefiore CTRC Ketamine: Subjects in the intervention arm will receive bolus and infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation. For the weaning population, they will receive a 12 hour infusion in the CTRC and stay an additional 12 hours in the CTRC (or until discharged). Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and for 12 hours after infusion discontinuation.

Relative Infant Dose of Ketamine (RID KET)

0.0152 % Maternal ketamine in breastmilk Standard Deviation 0.02

PRIMARY outcome

Timeframe: 27 hours postpartum or 24 hour CTRC appointment for weaning population

Relative infant dose (RID) will be calculated as the percentage of the maternal ketamine dose found from breastmilk. The relative infant dose was calculated from the concentrations of ketamine and its metabolites (ketamine, norketamine & dehydro-norketamine) in breast milk at different times following ketamine administration to the women.

Outcome measures

Measure

Ketamine n=8 Participants Ketamine - IV after cord clamping; IV infusion for 12 hours OR in the weaning population IV Ketamine infusion for 12 hours in the Montefiore CTRC Ketamine: Subjects in the intervention arm will receive bolus and infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation. For the weaning population, they will receive a 12 hour infusion in the CTRC and stay an additional 12 hours in the CTRC (or until discharged). Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and for 12 hours after infusion discontinuation.

Relative Infant Dose of Ketamine Equivalent (Ketamine, Norketamine, Dehydro-norketamine)

0.0217 % maternal dose in breast milk Standard Deviation 0.027

Adverse Events

Ketamine

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure

Ketamine n=8 participants at risk Ketamine - IV after cord clamping; IV infusion for 12 hours OR in the weaning population IV Ketamine infusion for 12 hours in the Montefiore CTRC Ketamine: Subjects in the intervention arm will receive bolus and infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation. For the weaning population, they will receive a 12 hour infusion in the CTRC and stay an additional 12 hours in the CTRC (or until discharged). Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and for 12 hours after infusion discontinuation.

Investigations Light Headedness

87.5% 7/8 • Number of events 7 • 6 months

Additional Information

Grace Lim, MD, MSc

UPMC

Phone: 412-641-1110

Email: limkg2@upmc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place