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A randomized non-inferiority trial of women with preeclampsia with severe features to determine if the addition of nonsteroidal anti-inflammatory drugs is inferior or non-inferior to standard analgesic bundles in their impact on postpartum hypertension.
Recently published clinical guidelines for the care of women with hypertensive disorders recommended that nonsteroidal anti-inflammatory drugs (NSAIDs) should be withheld from patients with hypertension that persists for more than one day postpartum (1). This recommendation is based in data from the general medicine literature, which suggests a role of NSAIDs in precipitating hypertension in non-pregnant adults (2,3). It may also draw from previously published case reports of post-partum hypertension that were thought to be NSAID induced (4). There has been a paucity of data from the obstetric literature to support or rebuff this recommendation. As the opioid crisis worsens in the United States, additional attention and resources have focused on limiting the use of narcotic medications. The effective employment of non-opioid analgesics has been shown to reduce narcotic use (5). Ibuprofen and other NSAIDs are the most effective and most commonly prescribed analgesics for postpartum pain, but clinicians now find themselves stuck between these recommendations and their efforts to limit unnecessary opioid prescriptions.
The investigators propose a randomized controlled non-inferiority trial of women with preeclampsia comparing a postpartum analgesic protocol that includes NSAIDs, to one that excludes them. The central hypothesis is that NSAID use does not worsen hypertensive diseases of pregnancy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NSAID Analgesic bundle | Experimental | Ibuprofen 600mg PO q 6 hrs as needed for pain, Acetaminophen 1000mg q 8 hrs as needed for pain, and Oxycodone 5 to 10 mg q 4 hrs as needed for pain. In patients undergoing cesarean section, ketorolac 30mg IV q 6 hrs may be substituted as an IV alternative to ibuprofen for the first 24 hours after surgery |
|
| NSAID free analgesic bundle | Active Comparator | Acetaminophen 1000mg q 8 hrs as needed for pain, and Oxycodone 5 to 10 mg q 4 hrs as needed for pain. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ibuprofen 600 mg | Drug | NSAID pain medication to be used in the experimental bundle for postpartum analgesia |
|
| Measure | Description | Time Frame |
|---|---|---|
| postpartum antihypertensive requirements | measurement of anti-hypertensive requirements at time of discharge | at the end of hospitalization, up to 7 days after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Postpartum pain scores | Evaluate the effect of NSAIDs on patient perception of pain | From randomization to 6 weeks after randomization |
| Postpartum opioid use | Compare the opioid requirements in each arm |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barnes Jewish Hospital | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24150027 | Background | Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-1131. doi: 10.1097/01.AOG.0000437382.03963.88. No abstract available. | |
| 23403779 | Background | Lo JO, Mission JF, Caughey AB. Hypertensive disease of pregnancy and maternal mortality. Curr Opin Obstet Gynecol. 2013 Apr;25(2):124-32. doi: 10.1097/GCO.0b013e32835e0ef5. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 9, 2019 | Jun 3, 2019 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 3, 2019 | Jun 3, 2019 | SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 12, 2019 | Jun 3, 2019 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D007052 | Ibuprofen |
| D020910 | Ketorolac |
| D000082 | Acetaminophen |
| D010098 | Oxycodone |
| ID | Term |
|---|---|
| D010666 | Phenylpropionates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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Randomized non-inferiority clinical trial
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| Ketorolac | Drug | NSAID analgesic to be used in the experimental bundle for postpartum analgesia in patients who underwent cesarean section |
|
| Acetaminophen | Drug | Analgesic medication to be used in both treatment arms |
|
| Oxycodone | Drug | Analgesic medication to be used in both treatment arms |
|
| From randomization to 6 weeks after randomization |
| Mean arterial blood pressure | Compare peak, average and median MAPs postpartum | From randomization to 6 weeks after randomization |
| End organ damage | Evaluate for evidence of renal, hepatic or neurological injury in the poatpartum period | during hospitalization, an average of 4 days |
| Hospital readmission | Evaluate the incidence of hospital readmission rate postpartum | From randomization to 6 weeks after randomization |
| Continued anti-hypertensive requirement | evaluate the need for antihypertensive medications at 6 weeks postpartum | up to 6 weeks |
| 15733721 | Background | Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005 Feb 26-Mar 4;365(9461):785-99. doi: 10.1016/S0140-6736(05)17987-2. |
| 29045342 | Background | Mogos MF, Salemi JL, Spooner KK, McFarlin BL, Salihu HH. Hypertensive disorders of pregnancy and postpartum readmission in the United States: national surveillance of the revolving door. J Hypertens. 2018 Mar;36(3):608-618. doi: 10.1097/HJH.0000000000001594. |
| 28885417 | Background | Viteri OA, England JA, Alrais MA, Lash KA, Villegas MI, Ashimi Balogun OA, Chauhan SP, Sibai BM. Association of Nonsteroidal Antiinflammatory Drugs and Postpartum Hypertension in Women With Preeclampsia With Severe Features. Obstet Gynecol. 2017 Oct;130(4):830-835. doi: 10.1097/AOG.0000000000002247. |
| D007213 |
| Indomethacin |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D000083 | Acetanilides |
| D000813 | Anilides |
| D000577 | Amides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D003061 | Codeine |
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |