Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT03260972 |
| Other study ID # |
IRB00129099 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
June 2021 |
| Est. completion date |
June 2023 |
Study information
| Verified date |
September 2021 |
| Source |
Johns Hopkins University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Objective The objective of this study is to test the hypothesis that instillation of
intra-abdominal chloroprocaine during cesarean deliveries is associated with decreased
postoperative pain and nausea compared to placebo, without increasing intraoperative and
postoperative complications.
Methods The investigators plan to randomize about 150 women undergoing primary and repeat
cesarean deliveries to intra-abdominal chloroprocaine versus placebo prior to abdominal
closure. Women will be excluded if they have ascertained or presumptive hypersensitivity to
the ester type and major anesthetics; if they have chronic pelvic pain or if they refuse to
participate in the study. The investigators' primary outcome measure will be postoperative
pain as measured by visual analogue scale (VAS) at 1 hour after skin closure. Secondary
outcomes will include objective pain as measured by VAS at 2, 6, 24 and 48 hours at rest and
during mobilization, adverse effects of chloroprocaine (gastrointestinal side effects,
pruritus), concomitant analgesic requirement, hospital readmissions and length of hospital
stay. Analysis will follow the intention-to-treat principle.
The investigators will also be studying the concentration/effect (PKPD) relationship of
chloroprocaine use for pain control in the postpartum period. The time courses of the plasma
concentrations of chloroprocaine will be analyzed with mixed effects
pharmacokinetic-pharmacodynamic (PKPD).
Description:
Postoperative pain relief is an important consideration during and after cesarean section.
Although many different methods have been described for proper pain relief, it remains not
sufficient and satisfactory in some patients.1,2 The overprescribing of opioids has reached a
critical level worldwide, and cesarean section may be the trigger for long-term opioid use in
many patients.1,2,3 The optimal strategy for perioperative pain control consists of
multimodal therapy to minimize the need for opioids, with the goals of perioperative pain
management being to relieve suffering, achieve early mobilization after surgery, reduce
length of hospital stay, and achieve patient satisfaction. Currently, most obstetricians use
a combination of opioids and NSAIDs for pain control postpartum. These pain control regimens
take into account medical, psychological, and physical condition of women, age, level of fear
or anxiety, allergies and personal preference at the time of cesarean section. Due to several
aspects such as maternal and neonatal wellbeing, postoperative pain relief in cesarean
delivery is crucial. Therefore, providing a proper regimen with very quick onset of action,
devoid of renal or gastrointestinal complications, and devoid of complications of neonatal
abstinence syndrome (NAS) becomes necessary.
Local anesthetics have been extensively used at the time of cesarean section. Chloroprocaine
(Nesacaine) is an ester-type local anesthetic (active ingredient - benzoic acid,
4-amino-2-chloro-2-(diethylamino) ethyl ester, monohydrochloride that has been used as an
anesthetic and analgesic in obstetrics & gynecology. It has a rapid onset time of action
(usually within 6 to 12 minutes; 9.6 min ± 7.3 min at 40 mg dose; 7.9 min ± 6.0 min at 50 mg
dose) and a motor block action lasting for 40 minutes to 2 hours.4 Chloroprocaine, like other
local anesthetics, blocks the generation and the conduction of nerve impulses, presumably by
increasing the threshold for electrical excitation in the nerve, by slowing the propagation
of the nerve impulse and by reducing the rate of rise of the action potential. In general,
the progression of anesthesia is related to the diameter, myelination and conduction velocity
of affected nerve fibers.
The rate of intra-abdominal chloroprocaine absorption is dependent upon the total dose and
concentration administered and the presence or absence of epinephrine in the anesthetic
injection. Epinephrine usually reduces the rate of absorption and plasma concentration of
local anesthetics and is sometimes added to local anesthetic injections in order to prolong
the duration of action. Various pharmacokinetic parameters of chloroprocaine can be
significantly altered by the presence of hepatic or renal disease, addition of epinephrine,
factors affecting urinary pH, renal blood flow, and the age of the patient. Chloroprocaine is
rapidly metabolized in plasma by hydrolysis of the ester linkage by pseudocholinesterase. The
hydrolysis of chloroprocaine results in the production of ß-diethylaminoethanol and
2-chloro-4-aminobenzoic acid, which inhibits the action of the sulfonamides. The kidney is
the main excretory organ for chloroprocaine and its metabolites. Urinary excretion is
affected by urinary perfusion and factors affecting urinary pH. Due to its short duration of
action, favorable safety profile, and very low toxicity, it has been used extensively for
spinal anesthesia at the time of cesarean section.5,6 It has also been used for skin
infiltration to reduce pain post cesarean section in patients who cannot receive spinal
analgesia due to contraindications.7 However, despite its advantages as an analgesic and
anesthetic, it has never clinically evaluated to be used intra-abdominally at the time of
cesarean section. Although its occasional use has been considered and employed in certain
clinical circumstances, clinical evaluation has not been attempted.
The goal of this study is to employ a well-designed randomized controlled clinical trial to
compare the efficacy of intraabdominal chloroprocaine administration versus placebo (sterile
saline) for pain control at the time of cesarean section. The investigators hypothesize that
intra-abdominal chloroprocaine administration at the time of cesarean delivery is associated
with decreased postoperative pain and nausea compared to non-administration of
chloroprocaine. Patients admitted for cesarean section and meeting inclusion criteria will be
approached for consent. Consented patients will then be randomized into two groups.
Group 1: (intraabdominal chloroprocaine administration): These participants will have
intraabdominal chloroprocaine administration at the time of cesarean section before fascial
closure.
Group 2: (Intraabdominal instillation of placebo (sterile saline): These participants will
have placebo (sterile saline) administered at the time of cesarean delivery before fascial
closure. Cesarean delivery will continue traditionally, including fascial and skin closure.
Assignment will be performed by opening a sequentially numbered opaque envelope containing
computer-randomized individual allocations. The envelope will be opened by the circulation
nurse in the operating room and silently viewed by the surgeons prior to surgery.
Instructions will be given to not verbalize the treatment arm revealed. The original
randomization will be performed by research staff before the initiation of the study using a
random number table generator, and the participants will be blinded to treatment once
assigned. Information regarding basic demographic data, interventions during the cesarean
delivery and postpartum course will be obtained from the participant's charts after discharge
from the hospital. The patients will be assessed for pain control, nausea and vomiting after
cesarean section. The protocol for labor management and fetal monitoring will be the same for
both groups, including continuous electronic fetal monitoring prior to delivery.
Both groups will undergo inspection of the uterine incision, with or without closure of the
vesicouterine peritoneum (bladder flap), abdominal peritoneum, or rectus muscles per
attending preference. Both groups will undergo standard closure of the abdominal fascia,
consisting of suturing with a running non locking delayed absorbable suture. Irrigation of
the subcutaneous tissues superior to the closed fascia will be performed in both groups.
Staples or absorbable suture will be used for skin closure. In addition, all participants
will receive a standardized dose of 1-2 g cefazolin intravenously as antibiotic prophylaxis
before the start of surgery. Participants with cefazolin allergy will receive 900 mg
clindamycin.
