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HealthyPhase 4NCT01943565

Intrathecal Hydromorphone for Post-cesarean Delivery Pain - a Dose Finding Study

A Phase 4 study testing Hydromorphone 25mcg, Hydromorphone 50mcg and Hydromorphone 100mcg in people with Healthy and Pain, run by Brigham and Women's Hospital at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Pain relief after cesarean delivery can be provided in a few ways. Most commonly, certain medications called opioids, such as morphine, are given through the vein or into the muscle. Read more about this study

Who is it for?
Ages 18 to 40 years, women onlyHealthy volunteers can take part
Conditions the study is for
Healthy, Pain, Pregnancy
What is being tested?
Hydromorphone 25mcg, Hydromorphone 50mcg and Hydromorphone 100mcg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteUnited States
Study dates
Dec 2014to Aug 2016
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 40 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy at-term parturients undergoing elective cesarean delivery under spinal anesthesia

Who cannot join

  • Emergency cesarean delivery
  • Respiratory disease
  • significant comorbidities: preeclampsia, insulin-dependent diabetes mellitus
  • obstructive sleep apnea
  • body mass index > 35kg/m2
  • <18yrs
  • documented intolerance or allergy to systemic or neuraxial opioids
  • patient with a history of chronic opioid or current use of opioids

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Pain relief after cesarean delivery can be provided in a few ways. Most commonly, certain medications called opioids, such as morphine, are given through the vein or into the muscle. However, a more effective way to give pain relief with fewer side effects (such as nausea and slowing your breathing) is to give opioids in the spinal space as part of the medications given for a cesarean delivery.

For many years, the opioid of choice was morphine due to its long anesthetic effect and acceptable side effect profile. A nation-wide disruption in the supply of preservative-free morphine has made it necessary to look for alternatives. Many institutions worldwide have used another opioid, called hydromorphone, in the spinal space for over a decade. This drug has a very good safety and side effect profile and has been used at the investigators' institution for more than a year. Of interest, while a number of different doses of hydromorphone have been used, there have been very few studies to evaluate the best dose for providing good pain relief with minimal side effects. The goal of this study is to find the best dose of spinal hydromorphone for women undergoing cesarean delivery.

Read the detailed description

Intrathecal opioids in have been shown to produce analgesia. Lipid solubility and effect on specific mu opioid receptors in the dorsal horn of the spinal cord primarily determine the analgesic effect of intrathecally injected opioids. Rostral spread of intrathecal opioids causes some of the side effects like pruritus, respiratory depression, nausea and vomiting.

In the investigators' institute, during cesarean delivery under spinal anesthesia is usually performed with 1.6-1.8 ml of 0.75% bupivacaine with dextrose (hyperbaric solution) with 10-20mcg of fentanyl. Preservative free intrathecal (IT) morphine100 to 200 mcg is injected at the time of initiation of spinal block for postoperative pain relief. Multiple studies have shown excellent postoperative pain relief following cesarean delivery up to 18hrs with this dosing regimen.

However, there has been a national shortage of preservative free morphine since August 2012. Based on the pharmacokinetic and pharmacodynamic profile, intrathecal (IT) preservative free hydromorphone 100 mcg has been used as a substitute. Anecdotal experience during the past 8 months suggest that patients have comparable post partum pain relief, with a similar side-effect profile to IT morphine.

There is no published data on the optimal dose of IT hydromorphone for post cesarean analgesia. There are case reports and retrospective case study of use of 100mcg IT hydromorphone. One randomized controlled trial for knee arthroscopy used 2.5-5-10 mcg of IT hydromorphone for postoperative analgesia.

Hence it is important to determine the optimal dose of IT hydromorphone for post operative pain management following cesarean delivery in terms of analgesic efficacy, incidence of side effects and the need for treatment interventions

This study will aim to determine the optimal dose of intrathecal hydromorphone that would provide adequate postoperative analgesia with minimal side effects.

Conditions
Healthy, Pain, Pregnancy
Being tested
Hydromorphone 25mcg, Hydromorphone 50mcg, Hydromorphone 100mcg, spinal anesthesia
Keywords
Pregnancy, Healthy, Intrathecal, Opioids, Spinal, Anesthesia, Pain, Cesarean, Delivery, Human
Medical subject headings
Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hydromorphone 25mcgDrug

    Also called HM25

    Intrathecal Hydromorphone 25mcg

  • Hydromorphone 50mcgDrug

    Also called HM50

    Intrathecal Hydromorphone 50mcg

  • Hydromorphone 100mcgDrug

    Also called HM100

    Intrathecal Hydromorphone 100mcg

  • spinal anesthesiaDrug

    bupivacaine 0.75% 1.6 mL (12mg)

Study groups in NCT01943565
Study groupRoleWhat they receive
Hydromorphone 25mcgActive comparatorThe arm will receive 25mcg intrathecal hydromorphone to supplement the spinal anesthesia
Receives: Drug: Hydromorphone 25mcg; Drug: spinal anesthesia
Hydromorphone 50mcgActive comparatorThe arm will receive 50mcg intrathecal hydromorphone to supplement the spinal anesthesia
Receives: Drug: Hydromorphone 50mcg; Drug: spinal anesthesia
Hydromorphone 100mcgActive comparatorThe arm will receive 100mcg intrathecal hydromorphone to supplement the spinal anesthesia
Receives: Drug: Hydromorphone 100mcg; Drug: spinal anesthesia

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 24hr Post-partum IV Opioid Requirement

    Intrathecal (IT) hydromorphone added to intrathecally administered local anesthetics for spinal anesthesia increases patient comfort by decreasing post-operative pain. This leads to a decrease in the post-operative intravenous hydromorphone requirements.

    Measured: 24hrs after administration of intrathecal hydromorphone

Secondary outcomes (7)

  1. Oxygen Saturation, Need for Supplemental Oxygen

    Intravenously, and to a lesser extent, intrathecally administered opioids can lead to respiratory depressions. Therefore the subjects' oxygen saturation is measured (standard clinical practice).

    Measured: 24hrs post administration of IT hydromorphone

  2. Patients With Nausea and Vomiting Requiring Rescue Medication

    IV and IT opioids can induce nausea and vomiting. Outcome measure is reported as percentage of patients with nausea and vomiting requiring rescue medication.

    Measured: 24hrs post administration of IT hydromorphone

  3. Number of Patients With Hypothermia (Body Temperature < 95F/35C)

    intrathecally administered opioids can cause hypothermia (body temperature <95F/35C)

    Measured: 24hrs post administration of IT hydromorphone

  4. Number of Patients With Visual Disturbances

    IT/IV opioids can create visual disturbances. The number of patients with visual disturbances are reported.

    Measured: 24hrs post administration of IT hydromorphone

  5. Number of Patients With Pruritus

    IT opioids can cause pruritus. Persistent pruritus requiring treatment will be recorded.

    Measured: 24hrs post administration of IT hydromorphone

  6. Intraoperative Vasopressor Use: Ephedrine Equivalents

    IT (intrathecal) applied local anesthetics and opioids can cause arterial and venous vasodilation leading to a decrease in afterload as well as preload. This is typically treated with volume replacement and vasopressors (acutely). Total intraoperative vasopressor use will be reported for ephedrine equivalents.

    Measured: Intraoperatively (at time of operation)

  7. Intraoperative Vasopressor Use: Phenylephrine Equivalents

    IT (intrathecal ) applied local anesthetics and opioids can cause arterial and venous vasodilation leading to a decrease in afterload as well as preload. This is typically treated with volume replacement and vasopressors (acutely).

    Total intraoperative vasopressor use will be reported for phenylephrine equivalents.

    Measured: Intraoperatively (at time of operation)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2013 (estimated)
  2. Study startDec 2014
  3. Primary completionJul 2016
  4. Study completionAug 2016

Why it stopped: Research question answered by another group of researchers (Sviggum et al)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01943565
Sponsor's protocol ID
2013P001850
Other IDs
Hydromorphone_IT
Status last verified
May 2017
First submitted
12 Sep 2013
Last updated
19 Jun 2017
Data monitoring committee
No

Publications

  • Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology. 1979 Feb;50(2):149-51. doi: 10.1097/00000542-197902000-00013. No abstract available.

    PubMed 373503

  • Ross BK, Hughes SC. Epidural and spinal narcotic analgesia. Clin Obstet Gynecol. 1987 Sep;30(3):552-65. doi: 10.1097/00003081-198709000-00010. No abstract available.

    PubMed 2888557

  • Palmer CM, Emerson S, Volgoropolous D, Alves D. Dose-response relationship of intrathecal morphine for postcesarean analgesia. Anesthesiology. 1999 Feb;90(2):437-44. doi: 10.1097/00000542-199902000-00018.

    PubMed 9952150

  • Milner AR, Bogod DG, Harwood RJ. Intrathecal administration of morphine for elective Caesarean section. A comparison between 0.1 mg and 0.2 mg. Anaesthesia. 1996 Sep;51(9):871-3. doi: 10.1111/j.1365-2044.1996.tb12622.x.

    PubMed 8882255

  • Lee YS, Park YC, Kim JH, Kim WY, Yoon SZ, Moon MG, Min TJ. Intrathecal hydromorphone added to hyperbaric bupivacaine for postoperative pain relief after knee arthroscopic surgery: a prospective, randomised, controlled trial. Eur J Anaesthesiol. 2012 Jan;29(1):17-21. doi: 10.1097/EJA.0b013e3283476055.

    PubMed 21562420

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Hydromorphone 25mcg, Hydromorphone 50mcg and Hydromorphone 100mcg in people with Healthy and Pain, run by Brigham and Women's Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

24hr Post-partum IV Opioid Requirement (time frame: 24hrs after administration of intrathecal hydromorphone). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01943565, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2017.

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