NCT04037085: KINETIC

Ketamine to Improve Recovery After Cesarean Delivery - Part 1

Completed Phase 2 Results posted Last updated 20 December 2022

What this trial tests

Phase 2 trial testing Ketamine in Obstetric Pain in 8 participants. Completed in 1 August 2021.

Timeline

9 October 2019

Primary endpoint
1 August 2021

1 August 2021

Quick facts

Lead sponsor	Grace Lim, MD, MS
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	prevention
Enrollment	8
Start date	9 October 2019
Primary completion	1 August 2021
Estimated completion	1 August 2021
Sites	2 locations across United States

Drugs / interventions tested

• Ketamine (ketamine) — full drug profile →

Conditions studied

• Obstetric Pain — all drugs for Obstetric Pain →
• Postpartum Depression — all drugs for Postpartum Depression →
• Breastfeeding — all drugs for Breastfeeding →
• Pain, Acute — all drugs for Pain, Acute →

Sponsor

Grace Lim, MD, MS — full company profile →

Who can join

Adults 18 to 99, female only, with Obstetric Pain or Postpartum Depression. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Ketamine (AUC) Primary · 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.

Group	Value	95% CI
Ketamine	28.46	± 9.97

Steady State (Css) Primary · 12 hours after ketamine infusion start

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

Group	Value	95% CI
Ketamine	35.58

Elimination Half Life (T1/2) for Ketamine Primary · 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.

Group	Value	95% CI
Ketamine	364	± 121

Volume of Distribution Steady State (Vdss) Primary · 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.

Group	Value	95% CI
Ketamine	1076	± 617

Ketamine Milk to Plasma Ratio (M:P) Primary · 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.

Group	Value	95% CI
Ketamine	3.15	± 1.05

Nor-ketamine Milk to Plasma Ratio Primary · 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.

Group	Value	95% CI
Ketamine	1.5	± 0.19

Hydroxynorketamine M:P Ratio Primary · 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.

Group	Value	95% CI
Ketamine	0.06	± 0.015

Relative Infant Dose of Ketamine (RID KET) Primary · 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.

Group	Value	95% CI
Ketamine	0.0152	± 0.02

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

Group	Value	95% CI
% RID Ketamine Equivalent (Ketamine, Norketamine, and Dehydronorketamine)	0.0217	± 0.027

Adverse events — posted to ClinicalTrials.gov

Time frame: 6 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ketamine

Serious: 0/8 (0%)

Deaths: 0/8

Other adverse events (1 terms — click to expand)

Reaction	System	Ketamine
Light Headedness	Investigations	—

Data from ClinicalTrials.gov NCT04037085 adverse events section.

Sponsor's own description

The objective of this study is evaluate the breastmilk transfer and pharmacokinetics (Part 1) and effectiveness (Part 2) of a post-cesarean delivery intravenous ketamine bolus-and-infusion strategy, as a preventive analgesic modality to reduce pain and opioid requirements.

In Part 1, physiochemical analysis of pharmacokinetic/pharmacodynamic (PK/PD) and breastmilk transfer of ketamine and its metabolites will be assessed. Additionally calculated estimations for neonatal and infant exposure will be assessed.

In Part 2, PK/PD assessments will continue in a larger cohort; endpoints will also include postpartum pain, depression scores, central sensitization measures, patient-reported postpartum recovery scores, breastfeeding, and parent-infant bonding, assessed in the acute post-cesarean period and up to 12 weeks postpartum in a randomized controlled trial.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.