The CHIPS Trial (Control of Hypertension In Pregnancy Study)

• ClinicalTrials.gov Identifier: NCT01192412
• Recruitment Status: Completed
• First Posted: September 1, 2010
• Results First Posted: January 11, 2017
• Last Update Posted: January 11, 2017
• Sponsor: University of British Columbia
• Collaborators: Canadian Institutes of Health Research (CIHR); Sunnybrook Research Institute
• Information provided by (Responsible Party): University of British Columbia

Tracking Information

• First Submitted Date: August 30, 2010
• First Posted Date: September 1, 2010
• Results First Submitted Date: August 30, 2016
• Results First Posted Date: January 11, 2017
• Last Update Posted Date: January 11, 2017
• Study Start Date: April 2009
• Actual Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 15, 2016)

Pregnancy Loss or NICU Admission for Greater Than 48 Hours [ Time Frame: 6 weeks ]

Pregnancy loss or NICU admission for greater than 48 hours, as recorded in the maternal and infant medical records immediately following the birth (or pregnancy loss), and then again after the mothers' and infants' discharge home. Supplemental information, about potential post-discharge maternal or neonatal morbidities in the 6 weeks following birth for the mother, or 28 days of life for the baby, will be obtained by contacting women at 6 weeks postpartum and/or from medical records.

Original Primary Outcome Measures (submitted: August 31, 2010)

Pregnancy loss or NICU admission for greater than 48 hours [ Time Frame: 6 weeks ]

Pregnancy loss or NICU admission for greater than 48 hours, as recorded in the maternal and infant medical records immediately following the birth (or pregnancy loss), and then again after the mothers' and infants' discharge home. Supplemental information, about potential post-discharge maternal or neonatal morbidities in the 6 weeks following birth for the mother, or 28 days of life for the baby, will be obtained by contacting women at 6 weeks postpartum and/or from medical records.

Current Secondary Outcome Measures (submitted: November 15, 2016)

Serious Maternal Complications Measured up to 6 Weeks Postpartum [ Time Frame: 6 weeks ]

Serious maternal complications measured up to 6 weeks postpartum. Death or one or more life-threatening maternal complications:

1. Adverse neurological complications (stroke, eclampsia, and/or blindness), and/or
2. End-organ failure (uncontrolled hypertension, inotropic support, pulmonary oedema, respiratory failure, myocardial ischaemia/infarction, renal failure, coagulopathy, and/or transfusion)

Original Secondary Outcome Measures (submitted: August 31, 2010)

Serious maternal complications measured up to 6 weeks postpartum [ Time Frame: 6 weeks ]

Serious maternal complications measured up to 6 weeks postpartum. Death or one or more life-threatening maternal complications:

1. Adverse neurological complications (stroke, eclampsia, and/or blindness), and/or
2. End-organ failure (uncontrolled hypertension, inotropic support, pulmonary oedema, respiratory failure, myocardial ischaemia/infarction, renal failure, coagulopathy, and/or transfusion)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The CHIPS Trial (Control of Hypertension In Pregnancy Study)
• Official Title: The CHIPS Trial (Control of Hypertension In Pregnancy Study)

Brief Summary

The investigators do not know which approach to treatment of non-severe high blood pressure in pregnancy is better for women and babies.

In the CHIPS Trial, the investigators seek to determine whether 'less tight' control (aiming for a diastolic blood pressure [dBP] of 100 mmHg), compared with 'tight' control (aiming for a diastolic blood pressure [dBP] of 85 mmHg) can decrease the risks of adverse baby outcomes without increasing the risk of problems for the mother.

Detailed Description

Primary research question:

For pregnant women with non-severe, non-proteinuric maternal hypertension at 14-33 weeks, will 'less tight' control (target diastolic blood pressure [dBP] of 100 mmHg) versus 'tight' control (target dBP of 85 mmHg) increase (or decrease) the likelihood of pregnancy loss or Neonatal Intensive Care Unit (NICU) admission for greater than 48 hours?

Secondary research question:

Will 'less tight' versus 'tight' control increase (or decrease) the likelihood of serious maternal complications?

Other research questions:

Will 'less tight' versus 'tight' control:

1. Increase (or decrease) the likelihood of serious perinatal complications?
2. Increase (or decrease) the likelihood of severe hypertension and pre-eclampsia?
3. Increase (or decrease) the likelihood of maternal satisfaction with care?
4. Result in significant changes in dBP or health care costs?

Treatment Allocation:

Eligible women will be randomised centrally to either 'less tight' control (aiming for dBP of 100mmHg) or 'tight' control (aiming for dBP of 85mmHg) of their hypertension.

Randomisation will be stratified by centre and type of hypertension (pre-existing or gestational).

• In the 'less tight' control group, if dBP is ≥105mmHg, then antihypertensive medication must be started or increased in dose.
• In the 'tight' control group, if dBP is ≤80mmHg, then antihypertensive medication must be decreased in dose or discontinued.
• In both groups, centres will provide their usual care. Data will be collected on potential co-interventions (e.g., hospitalisation, bedrest).

Outcomes:

Primary: Pregnancy loss (miscarriage or ectopic pregnancy, pregnancy termination, stillbirth, or neonatal death) or high level neonatal care for >48 hours in the first 28 days of life or prior to primary hospital discharge, whichever is later.

Secondary: One/more serious maternal complication(s) until six weeks postpartum.

Follow-up:

Compliance (dBP and antihypertensive dose) will be assessed within 4 weeks of randomisation. Outcome data will be collected during the woman's (and baby's) hospital stay for birth (or loss). Women will be contacted 6 to 12 weeks after delivery (or loss) and, for preterm babies, when the baby is at 36 weeks corrected gestational age to enquire about satisfaction with care and any major maternal/neonatal morbidity following hospital discharge.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Gestational Hypertension

Intervention

• Procedure: Intervention is blood pressure management approach
  1) 'Less tight' control. The dBP treatment goal is 100 mmHg. For safety, if dBP is >105 mmHg, then antihypertensive medication must be started or increased in dose. For dBP <100 mmHg, antihypertensive therapy should be decreased in dose or stopped, as appropriate. The intervention will be applied until delivery.
• Procedure: Intervention is blood pressure management approach.
  'Tight' control. The dBP treatment goal is 85 mmHg. For safety, if dBP is <80 mmHg, then antihypertensive medication must be decreased in dose or discontinued. If dBP is >85 mmHg, then antihypertensive therapy should be started or increased in dose. The intervention will be applied until delivery.

Study Arms

• Active Comparator: 'Less tight' control.
  The diastolic blood pressure (dBP) treatment goal is 100 mmHg.
  Intervention: Procedure: Intervention is blood pressure management approach
• Active Comparator: 'Tight' control.
  The diastolic blood pressure (dBP) treatment goal is 85 mmHg.
  Intervention: Procedure: Intervention is blood pressure management approach.

Publications *

• Magee LA, Singer J, Lee T, McManus RJ, Lay-Flurrie S, Rey E, Chappell LC, Myers J, Logan AG, von Dadelszen P. Are blood pressure level and variability related to pregnancy outcome? Analysis of control of hypertension in pregnancy study data. Pregnancy Hypertens. 2020 Jan;19:87-93. doi: 10.1016/j.preghy.2019.12.002. Epub 2020 Jan 9.
• Vidler M, Magee LA, von Dadelszen P, Rey E, Ross S, Asztalos E, Murphy KE, Menzies J, Sanchez J, Singer J, Gafni A, Gruslin A, Helewa M, Hutton E, Lee SK, Lee T, Logan AG, Ganzevoort W, Welch R, Thornton JG, Moutquin JM; CHIPS Study Group. Women's views and postpartum follow-up in the CHIPS Trial (Control of Hypertension in Pregnancy Study). Eur J Obstet Gynecol Reprod Biol. 2016 Nov;206:105-113. doi: 10.1016/j.ejogrb.2016.07.509. Epub 2016 Sep 10.
• Magee LA, von Dadelszen P, Singer J, Lee T, Rey E, Ross S, Asztalos E, Murphy KE, Menzies J, Sanchez J, Gafni A, Helewa M, Hutton E, Koren G, Lee SK, Logan AG, Ganzevoort W, Welch R, Thornton JG, Moutquin JM; CHIPS Study Group*. The CHIPS Randomized Controlled Trial (Control of Hypertension in Pregnancy Study): Is Severe Hypertension Just an Elevated Blood Pressure? Hypertension. 2016 Nov;68(5):1153-1159. doi: 10.1161/HYPERTENSIONAHA.116.07862. Epub 2016 Sep 12.
• Ahmed RJ, Gafni A, Hutton EK, Hu ZJ, Pullenayegum E, von Dadelszen P, Rey E, Ross S, Asztalos E, Murphy KE, Menzies J, Sanchez JJ, Ganzevoort W, Helewa M, Lee SK, Lee T, Logan AG, Moutquin JM, Singer J, Thornton JG, Welch R, Magee LA. The Cost Implications of Less Tight Versus Tight Control of Hypertension in Pregnancy (CHIPS Trial). Hypertension. 2016 Oct;68(4):1049-55. doi: 10.1161/HYPERTENSIONAHA.116.07466. Epub 2016 Aug 22.
• Magee LA, von Dadelszen P, Rey E, Ross S, Asztalos E, Murphy KE, Menzies J, Sanchez J, Singer J, Gafni A, Gruslin A, Helewa M, Hutton E, Lee SK, Lee T, Logan AG, Ganzevoort W, Welch R, Thornton JG, Moutquin JM. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med. 2015 Jan 29;372(5):407-17. doi: 10.1056/NEJMoa1404595.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 4, 2015): 987
• Original Estimated Enrollment (submitted: August 31, 2010): 1028
• Actual Study Completion Date: February 2014
• Actual Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Pre-existing or gestational hypertension (pre-existing hypertension is dBP greater than or equal to 90 mmHg before pregnancy or 20 weeks' gestation; gestational hypertension is dBP greater than or equal to 90 mmHg that develops after 20 weeks)
2. dBP of 90 - 105 mmHg if NOT TAKING antihypertensive therapy, or dBP of 85 - 105 mmHg if TAKING antihypertensive therapy
3. Live foetus (confirmed by Doptone assessment of foetal heart tones within one week before randomisation)
4. Gestational age 14 - 33+6 weeks (as measured by last menstrual period or dating ultrasound)

Exclusion Criteria:

1. Severe systolic hypertension (defined as a systolic blood pressure [sBP] greater than or equal to 160 mmHg at randomisation)
2. Proteinuria (defined as greater than or equal to 0.3 g/d by 24 hour urine collection, or if a 24 hour urine collection is not available, by a urinary protein:creatinine ratio of greater than or equal to 30 mg/mmol or urinary dipstick of greater than or equal to 2+)
3. Use of an angiotensin converting enzyme (ACE) inhibitor at greater than or equal to 14+0 weeks' gestation
4. Contraindication to either arm of the trial or to pregnancy prolongation
5. Known multiple gestation
6. Known lethal or major foetal anomaly
7. Plan to terminate pregnancy
8. Prior participation in CHIPS

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Brazil, Canada, Chile, Colombia, Estonia, Hungary, Israel, Jordan, Netherlands, New Zealand, Poland, United Kingdom, United States
• Removed Location Countries: Equatorial Guinea, Qatar

Administrative Information

• NCT Number: NCT01192412
• Other Study ID Numbers: H08-00882; MCT-87522 ( Other Grant/Funding Number: CIHR ); 07-3431 ( Other Identifier: UBC )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of British Columbia
• Original Responsible Party: Dr. Laura Ann Magee, The University of British Columbia
• Current Study Sponsor: University of British Columbia
• Original Study Sponsor: Same as current

Collaborators

• Canadian Institutes of Health Research (CIHR)
• Sunnybrook Research Institute

Investigators

• Principal Investigator: Laura A Magee, MD, FRCPC, MSc, FACP; The University of British Columbia

• PRS Account: University of British Columbia
• Verification Date: November 2016