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

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Gestational Hypertension
• Interventions: Procedure: Intervention is blood pressure management approach; Procedure: Intervention is blood pressure management approach.
• Enrollment: 987

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	'Less Tight' Control.	'Tight' Control.
Arm/Group Description	The diastolic blood pressure (dBP) treatment goal is 100 mmHg. 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.	The diastolic blood pressure (dBP) treatment goal is 85 mmHg. 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.
Period Title: Overall Study
Started	497	490
Completed	493	488
Not Completed	4	2
Reason Not Completed
Lost to Follow-up	2	1
Withdrawal by Subject	2	1

Baseline Characteristics

Arm/Group Title		'Less Tight' Control.	'Tight' Control.	Total
Arm/Group Description		The diastolic blood pressure (dBP) treatment goal is 100 mmHg. 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.	The diastolic blood pressure (dBP) treatment goal is 85 mmHg. 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.	Total of all reporting groups
Overall Number of Baseline Participants		497	490	987
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	497 participants	490 participants	987 participants
		34.0 (5.7)	33.7 (5.8)	33.8 (5.8)
Gender; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	497 participants	490 participants	987 participants
	Female	497 100.0%	490 100.0%	987 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Body-mass index [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	497 participants	490 participants	987 participants
<18.5 kg/m^2		1	2	3
18.5-24.9 kg/m^2		116	112	228
25.0-29.9 kg/m^2		131	135	266
≥30.0 kg/m^2		245	236	481
		[1] Measure Description: Available in 493 women in 'Less-tight' control, and 485 women in 'Tight' control
Cigarette smoking during this pregnancy; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	497 participants	490 participants	987 participants
		35	28	63
Nulliparous [1]; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	497 participants	490 participants	987 participants
		161	168	329
		[1] Measure Description: Women who were never pregnant before (i.e., first pregnancy)
Weeks of gestation; Mean (Standard Deviation); Unit of measure: Weeks
	Number Analyzed	497 participants	490 participants	987 participants
		23.7 (6.3)	24.2 (6.3)	23.9 (6.3)
Type of nonproteinuric hypertension; Measure Type: Number; Unit of measure: Participants	Number Analyzed	497 participants	490 participants	987 participants
Preexisting hypertension		371	365	736
Gestational hypertension		126	125	251
Prior blood pressure ≥160 mm Hg systolic or ≥110 mm Hg diastolic during this pregnancy; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	497 participants	490 participants	987 participants
		82	59	141
Antihypertensive medication at enrollment; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	497 participants	490 participants	987 participants
		279	287	566
Blood pressure within 1 wk before randomization; Mean (Standard Deviation); Unit of measure: mmHg	Number Analyzed	497 participants	490 participants	987 participants
Systolic		140.4 (9.7)	139.7 (9.8)	140.1 (9.8)
Diastolic		92.6 (4.8)	92.2 (5.2)	92.4 (5.0)
Currently monitoring blood pressure at home; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	497 participants	490 participants	987 participants
		185	194	379
Gestational diabetes at enrollment; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	497 participants	490 participants	987 participants
		32	31	63

Outcome Measures

1. Primary Outcome

Title	Pregnancy Loss or NICU Admission for Greater Than 48 Hours
Description	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.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	'Less Tight' Control.	'Tight' Control.
Arm/Group Description:	The diastolic blood pressure (dBP) treatment goal is 100 mmHg. 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.	The diastolic blood pressure (dBP) treatment goal is 85 mmHg. 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.
Overall Number of Participants Analyzed	493	488
Measure Type: Number; Unit of Measure: participants
	155	150

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	'Less Tight' Control., 'Tight' Control.
	Comments	We estimated that with a sample size of 514 per group, the study would have 80% power, at a two-tailed alpha level of 0.05, assuming primary outcome rates of 33% in the tight-control group and 25% in the less-tight-control group, a 10% rate of crossover, a 1% loss to follow-up, and two interim analyses, as calculated with the chi-square test with the use of East software (Cytel) and the Lan-DeMets spending function with O'Brien-Fleming-type boundaries for early stopping.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.35
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Serious Maternal Complications Measured up to 6 Weeks Postpartum
Description	Serious maternal complications measured up to 6 weeks postpartum. Death or one or more life-threatening maternal complications: Adverse neurological complications (stroke, eclampsia, and/or blindness), and/or; End-organ failure (uncontrolled hypertension, inotropic support, pulmonary oedema, respiratory failure, myocardial ischaemia/infarction, renal failure, coagulopathy, and/or transfusion)
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	'Less Tight' Control.	'Tight' Control.
Arm/Group Description:	The diastolic blood pressure (dBP) treatment goal is 100 mmHg. 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.	The diastolic blood pressure (dBP) treatment goal is 85 mmHg. 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.
Overall Number of Participants Analyzed	493	488
Measure Type: Number; Unit of Measure: participants
	18	10

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	'Less Tight' Control., 'Tight' Control.
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.74
	Confidence Interval	(2-Sided) 95%; 0.79 to 3.84
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	'Less Tight' Control.	'Tight' Control.
Arm/Group Description	The diastolic blood pressure (dBP) treatment goal is 100 mmHg. 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.	The diastolic blood pressure (dBP) treatment goal is 85 mmHg. 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.
All-Cause Mortality
	'Less Tight' Control.	'Tight' Control.
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	'Less Tight' Control.	'Tight' Control.
	Affected / at Risk (%)	Affected / at Risk (%)
Total	155/493 (31.44%)	150/488 (30.74%)
Blood and lymphatic system disorders
Transfusion	16/493 (3.25%)	8/488 (1.64%)
Cardiac disorders
Uncontrolled hypertension	0/493 (0.00%)	0/488 (0.00%)
Nervous system disorders
Transient ischemic attack or stroke	0/493 (0.00%)	1/488 (0.20%)
Pregnancy, puerperium and perinatal conditions
Pregnancy loss	15/493 (3.04%)	15/488 (3.07%)
Miscarriage	0/493 (0.00%)	1/488 (0.20%)
Ectopic pregnancy	0/493 (0.00%)	0/488 (0.00%)
Elective termination	1/493 (0.20%)	1/488 (0.20%)
Perinatal death	14/493 (2.84%)	11/488 (2.25%)
Stillbirth	12/493 (2.43%)	7/488 (1.43%)
Neonatal death	2/493 (0.41%)	4/488 (0.82%)
High-level neonatal care for >48hr	141/480 (29.38%)	139/479 (29.02%)
Birthweight <10th percentile	79/491 (16.09%)	96/488 (19.67%)
Birthweight <3rd percentile	23/491 (4.68%)	26/488 (5.33%)
Renal and urinary disorders
Renal failure	0/493 (0.00%)	1/488 (0.20%)
Respiratory, thoracic and mediastinal disorders
Pulmonary edema	2/493 (0.41%)	1/488 (0.20%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	'Less Tight' Control.	'Tight' Control.
	Affected / at Risk (%)	Affected / at Risk (%)
Total	241/493 (48.88%)	223/488 (45.70%)
Cardiac disorders
Severe hypertension	200/493 (40.57%)	134/488 (27.46%)
Pregnancy, puerperium and perinatal conditions
Placental abruption	11/493 (2.23%)	11/488 (2.25%)
Preeclampsia	241/493 (48.88%)	223/488 (45.70%)

Limitations and Caveats

Women with preexisting or gestational hypertension included, and may have differing management. Primary/secondary outcomes included causes of pregnancy loss and interventions for neonatal care not expected to be associated with maternal BP control

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Laura A. Magee
• Organization: St. George's, University of London
• Phone: +442086729944 ext 52621
• EMail: LMagee@sgul.ac.uk

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of British Columbia
• ClinicalTrials.gov Identifier: NCT01192412
• Obsolete Identifiers: NCT01081171
• Other Study ID Numbers: H08-00882; MCT-87522 ( Other Grant/Funding Number: CIHR ); 07-3431 ( Other Identifier: UBC )
• First Submitted: August 30, 2010
• First Posted: September 1, 2010
• Results First Submitted: August 30, 2016
• Results First Posted: January 11, 2017
• Last Update Posted: January 11, 2017