Hypertension, Pregnancy-InducedPhase 4NCT02891174
The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
A Phase 4 study testing Ibuprofen and Acetaminophen in people with Hypertension, Pregnancy-Induced and Pre-eclampsia, run by University of Michigan at 1 site in United States.
Trial summary
To assess the effect of routine doses of ibuprofen on post-partum blood pressure control in women with gestational hypertension (gHTN) or preeclampsia without severe features (preE). Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Hypertension, Pregnancy-Induced, Pre-eclampsia
- What is being tested?
- Ibuprofen and Acetaminophen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2016to 20 Jun 2018
- 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 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Antepartum women
- Diagnosis of Gestational Hypertension or Pre-eclampsia by blood pressure ≥140 systolic or ≥90 diastolic, on at least 2 measurements ≥ 4 hours apart; with or without proteinuria (urine protein-creatinine ratio ≥0.3 or 24 hour-urine protein ≥300 mg).
- Taking one or fewer oral medications for blood pressure control.
- Singleton gestation.
- English-speaking
Who cannot join
- Allergy to nonsteroidal anti-inflammatory drugs, aspirin, or acetaminophen
- More than 1 severe range blood pressure (≥160 systolic or ≥110 diastolic) prior to enrollment.
- Neurologic symptoms attributed to hypertension (headache, visual changes) prior to enrollment.
- Pulmonary edema.
- Elevated AST (>60 international units/L) or ALT (>70 international units/L) prior to enrollment.
- Low platelet count (<100,000/microliter) prior to enrollment.
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- Renal insufficiency (creatinine > 1.1 or double the baseline creatinine if known) prior to enrollment.
- Chronic hypertension defined as hypertension pre-existing pregnancy or diagnosed prior to 20-weeks' gestation.
- Moderate- or severe-persistent asthma.
- Therapeutic anticoagulation.
- Chronic opiate use during the pregnancy (opiate therapy given daily for > 2 weeks).
- Lactose intolerance or allergy due to placebo containing lactose.
- Cesarean delivery.
- Additional anesthesia at time of delivery (spinal anesthesia, sedation) that would change routine pain management.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized-controlled Trial to Assess the Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
To assess the effect of routine doses of ibuprofen on post-partum blood pressure control in women with gestational hypertension (gHTN) or preeclampsia without severe features (preE).
Read the detailed description
Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for post-partum analgesia. This use is supported by limited data on post-partum pain specifically; however, ibuprofen and other NSAIDs are superior to acetaminophen in ameliorating uterine pain and cramping in dysmenorrhea. The effect of NSAIDs on blood pressure (BP) in women post-partum is less well-known. In non-pregnant hypertensive patients NSAIDs are associated with increased BP over short courses of days to months, though effects of various NSAIDs differ. Pooled analyses suggest changes in mean BP of up to 3-6 mm Hg depending on the measurement method.There are case reports of hypertensive crises after NSAID administration post-partum in both normotensive and hypertensive women. A larger, recent retrospective cohort study found no difference in mean arterial pressure (MAP) or need for antihypertensive therapy in women with severe hypertensive disorders of pregnancy who were exposed to NSAIDs post-partum.
In light of the potential for worsening blood pressure in women with hypertensive disorders of pregnancy, the Task Force on Hypertension in Pregnancy of American College of Obstetricians and Gynecologists stated that "providers should be reminded of the contribution of nonsteroidal anti-inflammatory agents to increased BP." Additionally the task force recommends that NSAIDS "be replaced by other analgesics in women with hypertension that persists for more than 1 day postpartum". However, provider practices since the publication of these guidelines have varied.
Hypothesis: When compared to acetaminophen, ibuprofen does not increase post-partum systolic blood pressure (SBP) above baseline to a clinically relevant degree (≥10 mmHg) in women with gHTN and preE.
Aim 1: To assess the mean difference in SBP during 24 hours of exposure to ibuprofen and acetaminophen.
Aim 2: To assess whether ibuprofen results in higher satisfaction with pain control in the immediate post-partum period (48 hours) compared to acetaminophen.
Aim 3: To prospectively assess the need for post-partum anti-hypertensive therapy and readmission for blood pressure control in women with gHTN and preE. The post-partum period is defined as delivery through 6 weeks after delivery.
- Conditions
- Hypertension, Pregnancy-Induced, Pre-eclampsia
- Being tested
- Ibuprofen, Acetaminophen
- Keywords
- ibuprofen, acetaminophen, blood pressure, post-partum, pain control, pre-eclampsia, gestational hypertension
- Medical subject headings
- Hypertension, Pregnancy-Induced, Pre-Eclampsia, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbuprofenDrug
Also called Advil, Motrin
At the time of delivery, eligibility will be reviewed. If the participant remains eligible, she will be randomized by the study pharmacy to begin post-partum analgesic therapy with ibuprofen followed by acetaminophen.
AcetaminophenDrug
Also called Tylenol
At the time of delivery, eligibility will be reviewed. If the participant remains eligible, she will be randomized by the study pharmacy to begin post-partum analgesic therapy with acetaminophen followed by ibuprofen.
| Study group | Role | What they receive |
|---|---|---|
| Ibuprofen followed by acetaminophen | Active comparator | Ibuprofen administered immediately post-partum, 600 mg (3 x 200 mg tablets) every 6 hours for 24 hours followed by acetaminophen, 650 mg (2 x 325 mg tablets) every 6 hours for 24 hours. Receives: Drug: Ibuprofen; Drug: Acetaminophen |
| Acetaminophen followed by ibuprofen | Active comparator | Acetaminophen administered immediately post-partum, 650 mg (2 x 325 mg tablets) every 6 hours for 24 hours followed by ibuprofen, 600 mg (3 x 200 mg tablets) every 6 hours for 24 hours. Receives: Drug: Ibuprofen; Drug: Acetaminophen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Systolic Blood Pressure (SBP)
The adjusted mean difference in systolic blood pressure after 24 hours of exposure each to ibuprofen and acetaminophen.
Measured: 24 hours following intervention
Secondary outcomes (3)
Change in Self-reported Pain Score 2 Hours After First Intervention
Prior to the first dose of pain medication, participants will take a brief, self-administered survey to assess abdominal and overall pain using a 0-10 scale. Two hours after the first dose of study drug, participants will repeat the self-administered survey to assess abdominal, perineal, and overall pain using a 0-10 scale. Clinical Pain Scale: 0=no pain to 10=worst pain.
Measured: At the time of first dose of study drug and 2 hours after
Mean Pain Score by Nursing Assessment
Pain scores using a 0-10 scale as assessed by nursing during the 48 hours from initial study medication administration will be abstracted from the participant's medical record. Clinical Pain Scale: 0=no pain to 10=worst pain. All pain scores during the first intervention (0-24 hours) and second intervention (24-48) are included according to intention-to-treat principles.
Measured: 0-24 hours and 24-48 hours after initial study medication administration
Satisfaction With Pain Control During 24 Hours of Exposure Each to Ibuprofen and Acetaminophen
A brief survey on satisfaction with pain control during the first 24 hours post-partum and the second 24 hours post-partum, as well as overall during post-partum stay will be administered prior to discharge using a 1-5 Likert scale: 1=not satisfied to 5=extremely satisfied.
Measured: 24 hours and 48 hours after initial study medication administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2016 (estimated)
- Study start1 Dec 2016
- Primary completion31 Mar 2018
- Study completion20 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hypertension, Pregnancy-InducedStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elizabeth Langen, University of Michigan
- Investigators
- Jourdan Triebwasser, MD, Principal investigator, University of MichiganElizabeth Langen, MD, Principal investigator, University of MichiganAlexander Tsodikov, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02891174
- Sponsor's protocol ID
- HUM00117154
- Status last verified
- May 2019
- First submitted
- 26 Aug 2016
- Last updated
- 23 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized-controlled Trial to Assess the Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
- ClinicalTrials.gov ID
- NCT02891174
- Acronym / sponsor ID
- HUM00117154
- Conditions
- Hypertension, Pregnancy-Induced, Pre-eclampsia
- Keywords
- ibuprofen, acetaminophen, blood pressure, post-partum, pain control, pre-eclampsia, gestational hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Study start
- 1 Dec 2016 (actual)
- Primary completion
- 31 Mar 2018 (actual)
- Study completion
- 20 Jun 2018 (actual)
- First posted
- 7 Sep 2016 (estimated)
- Results
- Posted 23 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the effect of routine doses of ibuprofen on post-partum blood pressure control in women with gestational hypertension (gHTN) or preeclampsia without severe features (preE).
Detailed description
Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for post-partum analgesia. This use is supported by limited data on post-partum pain specifically; however, ibuprofen and other NSAIDs are superior to acetaminophen in ameliorating uterine pain and cramping in dysmenorrhea. The effect of NSAIDs on blood pressure (BP) in women post-partum is less well-known. In non-pregnant hypertensive patients NSAIDs are associated with increased BP over short courses of days to months, though effects of various NSAIDs differ. Pooled analyses suggest changes in mean BP of up to 3-6 mm Hg depending on the measurement method.There are case reports of hypertensive crises after NSAID administration post-partum in both normotensive and hypertensive women. A larger, recent retrospective cohort study found no difference in mean arterial pressure (MAP) or need for antihypertensive therapy in women with severe hypertensive disorders of pregnancy who were exposed to NSAIDs post-partum.
In light of the potential for worsening blood pressure in women with hypertensive disorders of pregnancy, the Task Force on Hypertension in Pregnancy of American College of Obstetricians and Gynecologists stated that "providers should be reminded of the contribution of nonsteroidal anti-inflammatory agents to increased BP." Additionally the task force recommends that NSAIDS "be replaced by other analgesics in women with hypertension that persists for more than 1 day postpartum". However, provider practices since the publication of these guidelines have varied.
Hypothesis: When compared to acetaminophen, ibuprofen does not increase post-partum systolic blood pressure (SBP) above baseline to a clinically relevant degree (≥10 mmHg) in women with gHTN and preE.
Aim 1: To assess the mean difference in SBP during 24 hours of exposure to ibuprofen and acetaminophen.
Aim 2: To assess whether ibuprofen results in higher satisfaction with pain control in the immediate post-partum period (48 hours) compared to acetaminophen.
Aim 3: To prospectively assess the need for post-partum anti-hypertensive therapy and readmission for blood pressure control in women with gHTN and preE. The post-partum period is defined as delivery through 6 weeks after delivery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ibuprofen followed by acetaminophen | Active comparator | Drug: Ibuprofen, Drug: AcetaminophenIbuprofen administered immediately post-partum, 600 mg (3 x 200 mg tablets) every 6 hours for 24 hours followed by acetaminophen, 650 mg (2 x 325 mg tablets) every 6 hours for 24 hours. |
| Acetaminophen followed by ibuprofen | Active comparator | Drug: Ibuprofen, Drug: AcetaminophenAcetaminophen administered immediately post-partum, 650 mg (2 x 325 mg tablets) every 6 hours for 24 hours followed by ibuprofen, 600 mg (3 x 200 mg tablets) every 6 hours for 24 hours. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Antepartum women
- Diagnosis of Gestational Hypertension or Pre-eclampsia by blood pressure ≥140 systolic or ≥90 diastolic, on at least 2 measurements ≥ 4 hours apart; with or without proteinuria (urine protein-creatinine ratio ≥0.3 or 24 hour-urine protein ≥300 mg).
- Taking one or fewer oral medications for blood pressure control.
- Singleton gestation.
- English-speaking
Key exclusion criteria (14 listed)
- Allergy to nonsteroidal anti-inflammatory drugs, aspirin, or acetaminophen
- More than 1 severe range blood pressure (≥160 systolic or ≥110 diastolic) prior to enrollment.
- Neurologic symptoms attributed to hypertension (headache, visual changes) prior to enrollment.
- Pulmonary edema.
- Elevated AST (>60 international units/L) or ALT (>70 international units/L) prior to enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbuprofenAlso: Advil, MotrinAt the time of delivery, eligibility will be reviewed. If the participant remains eligible, she will be randomized by the study pharmacy to begin post-partum analgesic therapy with ibuprofen followed by acetaminophen. | Drug | Acetaminophen followed by ibuprofen, Ibuprofen followed by acetaminophen |
| AcetaminophenAlso: TylenolAt the time of delivery, eligibility will be reviewed. If the participant remains eligible, she will be randomized by the study pharmacy to begin post-partum analgesic therapy with acetaminophen followed by ibuprofen. | Drug | Acetaminophen followed by ibuprofen, Ibuprofen followed by acetaminophen |
Primary outcome
Difference in Systolic Blood Pressure (SBP)
Time frame: 24 hours following intervention
The adjusted mean difference in systolic blood pressure after 24 hours of exposure each to ibuprofen and acetaminophen.
3 secondary outcomes
Change in Self-reported Pain Score 2 Hours After First Intervention
Time frame: At the time of first dose of study drug and 2 hours after
Mean Pain Score by Nursing Assessment
Time frame: 0-24 hours and 24-48 hours after initial study medication administration
Satisfaction With Pain Control During 24 Hours of Exposure Each to Ibuprofen and Acetaminophen
Time frame: 24 hours and 48 hours after initial study medication administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jourdan Triebwasser, MD principal investigator
University of Michigan
Elizabeth Langen, MD principal investigator
University of Michigan
Alexander Tsodikov, PhD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ibuprofen and Acetaminophen in people with Hypertension, Pregnancy-Induced and Pre-eclampsia, run by University of Michigan 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 5 inclusion and 14 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: finished, as of the sponsor's last update on 23 May 2019. 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 23 May 2019). 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?
Difference in Systolic Blood Pressure (SBP) (time frame: 24 hours following intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 May 2019.