CHAP (Chronic Hypertension and Pregnancy) trial
A large trial in the United States that asked whether women with mildly raised blood pressure before or early in pregnancy do better if they take blood pressure medicine to keep their pressure under 140/90, or if they take medicine only when their pressure becomes severe. Everyone knew which approach they were in.
Also called CHAP
- Study
- In this atlas
Overview
- Design
- Pragmatic, multicenter, open-label, randomized controlled trial in the United States. Women were randomly assigned either to treatment aimed at keeping blood pressure under 140/90 mm Hg (the active group) or to standard care, in which blood-pressure drugs were not given, or were stopped if already in use, unless severe hypertension appeared. The sample size was reduced from a planned 4700 to a final 2404; the monitoring board for data and safety agreed to the reduction. A blinded outcome adjudication committee reviewed suspected primary and selected secondary outcomes. Follow-up ran to 6 weeks after birth.
- Phase
- Phase 4
- Enrolled
- 2,408 women
- 2,408 women (registry enrollment, type ACTUAL)
- 2,419 women
- 2,404 women (final sample size approved by the data and safety monitoring board)
- 4,700 women (originally planned enrollment)
- Sponsor
- Not recorded
- Registry
-
NCT02299414
-
- Results reported in
- Started
- (actual)
- Primary completion
- (actual)
- Completion
- (actual)
- Countries
- United States
- Care setting
- Recruiting sites of the CHAP Trial Consortium in the United States (more than 70 per the Methods; 2419 women were randomized at 61 sites per the Results). The manuscript does not say whether the sites were clinics or hospitals.
- Registry status
- “COMPLETED”
Technical summary
Pragmatic, open-label, randomized trial (NCT02299414; phase 4 in the registry). 2408 women were enrolled (the Results text reports 2419 randomized and 2408 analysed). Primary outcome: a composite of pre-eclampsia with severe features, medically indicated preterm birth before 35 weeks, placental abruption, or fetal or neonatal death. Primary safety outcome: a birth weight under the 10th percentile for the baby’s gestational age (small for gestational age). The funder was the National Heart, Lung, and Blood Institute; the registry names the University of Alabama at Birmingham as lead sponsor (no record in this atlas yet). The registry start date (2015-06) and the manuscript’s screening period (from September 2015) differ; the registry date is the one recorded.
Arms
-
Active treatment to a goal below 140/90 mm Hg
Intervention Antihypertensive drug treatment for non-severe hypertension in pregnancy
Antihypertensive drugs started or continued to reach a blood-pressure goal below 140/90 mm Hg. The first-line drugs were labetalol or extended-release nifedipine, supplied by the trial investigators.
-
Standard (control) treatment
Intervention
No antihypertensive treatment unless severe hypertension developed (systolic 160 mm Hg or higher, or diastolic 105 mm Hg or higher). Treatment already under way was withheld or stopped at randomization.
Findings
Findings are grouped by the claim they support. Each group keeps its own population and follow-up, and each finding keeps its own denominator and time window. Not reported is not zero, and findings from different contexts are not combined.
In plain words
In the CHAP trial in the United States, women with mild chronic hypertension who enrolled before 23 weeks of pregnancy and were treated to a blood-pressure goal below 140/90 mm Hg had fewer of the combined serious pregnancy problems than women whose treatment was held back unless their blood pressure became severe. The combined outcome (pre-eclampsia with severe features, a medically indicated preterm birth before 35 weeks, placental abruption, or the death of the fetus or newborn) occurred in 353 of 1170 women with outcome data in the treated group (30.2%) and 427 of 1155 in the control group (37.0%). A separate analysis that fills in missing outcomes gave an adjusted risk ratio of 0.82 (95% CI 0.74 to 0.92).
- The same women as the maternal CHAP context, with the outcomes of their pregnancies. The primary composite combines a maternal event (pre-eclampsia with severe features up to 2 weeks after birth), pregnancy events (medically indicated preterm birth before 35 weeks and placental abruption) and a fetal or neonatal event (fetal or neonatal death). It is used only for the composite as the trial defined it and is never split by recipient.
- Recruiting sites of the CHAP Trial Consortium in the United States; see the maternal CHAP context.
- United States
- Pregnancy and the newborn period
- Gestational age Not reported
- Postnatal age Not reported
CHAP primary composite outcome Primary endpoint
353 of 1,170 women in the Active treatment to a goal below 140/90 mm Hg arm
- Measure
- Women with a primary-outcome event (count), complete-case analysis
- Value
- 353 women
- Reported as
- 353/1170 (30.2%)
- Interval
- Not applicable
- Denominator
- n = 1,170
- Time window
- No single period is stated for the composite. Pre-eclampsia up to 2 weeks after birth; fetal or neonatal death at under 28 days (Table 2 row label). The registry gives up to 90 days for neonatal death.
427 of 1,155 women in the Standard (control) treatment arm
- Measure
- Women with a primary-outcome event (count), complete-case analysis
- Value
- 427 women
- Reported as
- 427/1155 (37.0%)
- Interval
- Not applicable
- Denominator
- n = 1,155
- Time window
- No single period is stated for the composite. Pre-eclampsia up to 2 weeks after birth; fetal or neonatal death at under 28 days (Table 2 row label). The registry gives up to 90 days for neonatal death.
Active treatment to a goal below 140/90 mm Hg compared with Standard (control) treatment
- Measure
- Adjusted risk ratio, active treatment vs control (multiple imputation analysis with multivariable log-binomial regression, N = 2408; Table 2 footnote)
- Value
- 0.82 ratio
- Reported as
- 0.82 (0.74-0.92), P<0.001
- Interval
- 0.74 to 0.92
- Denominator
- Not applicable
- Time window
- No single period is stated for the composite. Pre-eclampsia up to 2 weeks after birth; fetal or neonatal death at under 28 days (Table 2 row label). The registry gives up to 90 days for neonatal death.
Caveats
Limitations. Open-label trial in one country, so women and clinicians knew the assigned strategy. The composite mixes a maternal event with pregnancy events and fetal or neonatal events; the sources do not split it by recipient and the atlas does not either. The percentages and counts come from the complete-case analysis (2325 of 2408 women had enough data); the adjusted risk ratio comes from a multiple-imputation analysis of all 2408. They are different analyses. The authors’ secondary composites of serious maternal complications and of severe neonatal complications did not show clear differences in the abstract; they are about the mother and the newborn separately, so they are not recorded here as claims of their own. Secondary results were not adjusted for multiplicity. For women with newly diagnosed hypertension and for a body-mass index of 40 or more, the risk ratios were close to 1.00 with wide intervals. About 12 women were screened for each woman randomized. The sample size was reduced from a planned 4700 women to a final 2404 that the data and safety monitoring board approved, and the abstract and the Methods word the upper blood-pressure limit differently (below 160/100 vs below 160 and below 105 mm Hg). The registry calls the primary outcome perinatal although it includes a maternal event.
Sources and citations (6)
-
Supports Treatment for Mild Chronic Hypertension during Pregnancy
- Locator
- Abstract, RESULTS, sentence 2
- How it applies
- PubMed abstract of the primary report.
- Retrieved
- Source effective date
- Not reported
- Source state
- Current
- Snapshot hash
0d4e3df2a54e7410e41088da17ab93607e2184d8c086a69f5d47053347f746fe- Reuse basis
- Bibliographic metadata and short factual extraction only. The PMC author manuscript states that it is available for text mining and may be used consistent with fair use, so it is not committed and quotations stay at 24 words or fewer. The PubMed abstract carries a publisher copyright notice, so only hashes are kept. The version of record is not redistributed.
-
Supports Treatment for Mild Chronic Hypertension during Pregnancy
- Locator
- Table 2, row Primary composite outcome
- How it applies
- NIH author manuscript (PMC9575330); available for text mining and fair use only; not checked against the version of record. Counts are complete-case; the first ratio is the multiple-imputation adjusted risk ratio.
- Retrieved
- Source effective date
- Not reported
- Source state
- Current
- Snapshot hash
ad310682ed3d8aaac7c162897fc3938d64372fc558622433e3c400aecde53559- Reuse basis
- Bibliographic metadata and short factual extraction only. The PMC author manuscript states that it is available for text mining and may be used consistent with fair use, so it is not committed and quotations stay at 24 words or fewer. The PubMed abstract carries a publisher copyright notice, so only hashes are kept. The version of record is not redistributed.
-
Background Treatment for Mild Chronic Hypertension during Pregnancy
- Locator
- Table 2, column headings and footnotes
- How it applies
- Shows which analysis each column comes from.
- Retrieved
- Source effective date
- Not reported
- Source state
- Current
- Snapshot hash
ad310682ed3d8aaac7c162897fc3938d64372fc558622433e3c400aecde53559- Reuse basis
- Bibliographic metadata and short factual extraction only. The PMC author manuscript states that it is available for text mining and may be used consistent with fair use, so it is not committed and quotations stay at 24 words or fewer. The PubMed abstract carries a publisher copyright notice, so only hashes are kept. The version of record is not redistributed.
-
Background Treatment for Mild Chronic Hypertension during Pregnancy
- Locator
- Abstract, RESULTS, sentence 4
- How it applies
- Secondary composites without clear differences.
- Retrieved
- Source effective date
- Not reported
- Source state
- Current
- Snapshot hash
0d4e3df2a54e7410e41088da17ab93607e2184d8c086a69f5d47053347f746fe- Reuse basis
- Bibliographic metadata and short factual extraction only. The PMC author manuscript states that it is available for text mining and may be used consistent with fair use, so it is not committed and quotations stay at 24 words or fewer. The PubMed abstract carries a publisher copyright notice, so only hashes are kept. The version of record is not redistributed.
-
Background Treatment for Mild Chronic Hypertension during Pregnancy
- Locator
- Results, Subgroup analyses
- How it applies
- Subgroups close to no difference; the trial was not powered for subgroups.
- Retrieved
- Source effective date
- Not reported
- Source state
- Current
- Snapshot hash
ad310682ed3d8aaac7c162897fc3938d64372fc558622433e3c400aecde53559- Reuse basis
- Bibliographic metadata and short factual extraction only. The PMC author manuscript states that it is available for text mining and may be used consistent with fair use, so it is not committed and quotations stay at 24 words or fewer. The PubMed abstract carries a publisher copyright notice, so only hashes are kept. The version of record is not redistributed.
-
Background Treatment for Mild Chronic Hypertension during Pregnancy
- Locator
- Discussion, para 3
- How it applies
- Open-label design and the screening ratio.
- Retrieved
- Source effective date
- Not reported
- Source state
- Current
- Snapshot hash
ad310682ed3d8aaac7c162897fc3938d64372fc558622433e3c400aecde53559- Reuse basis
- Bibliographic metadata and short factual extraction only. The PMC author manuscript states that it is available for text mining and may be used consistent with fair use, so it is not committed and quotations stay at 24 words or fewer. The PubMed abstract carries a publisher copyright notice, so only hashes are kept. The version of record is not redistributed.
In plain words
In CHAP the mothers were treated, and the safety question was the baby’s growth. Babies born small for their gestational age (birth weight below the 10th percentile) numbered 128 of 1146 with data in the treated group (11.2%) and 117 of 1124 in the control group (10.4%). The adjusted risk ratio was 1.04 (95% CI 0.82 to 1.31). The interval includes no difference, so the trial did not show a clear change in this safety outcome.
- Infants born to the women in the trial who had birth-weight data: 1146 in the treated group and 1124 in the control group in the complete-case analysis. The infants were exposed through their mothers’ treatment; they were not treated themselves. The women enrolled before 23 weeks, and the gestational age at birth was not restricted by the source.
- Births at CHAP sites in the United States; the manuscript does not describe the birth setting.
- United States
- Newborn, birth weight measured at birth
- Gestational age Not reported
- Postnatal age 0 days to 0 days
Small-for-gestational-age birth weight (CHAP safety outcome) Primary endpoint
128 of 1,146 infants in the Active treatment to a goal below 140/90 mm Hg arm
- Measure
- Infants with birth weight below the 10th percentile (count), complete-case analysis
- Value
- 128 infants
- Reported as
- 128/1146 (11.2%)
- Interval
- Not applicable
- Denominator
- n = 1,146
- Time window
- Birth
117 of 1,124 infants in the Standard (control) treatment arm
- Measure
- Infants with birth weight below the 10th percentile (count), complete-case analysis
- Value
- 117 infants
- Reported as
- 117/1124 (10.4%)
- Interval
- Not applicable
- Denominator
- n = 1,124
- Time window
- Birth
Active treatment to a goal below 140/90 mm Hg compared with Standard (control) treatment
- Measure
- Adjusted risk ratio, active treatment vs control (multiple imputation analysis with multivariable log-binomial regression, N = 2408; Table 2 footnote)
- Value
- 1.04 ratio
- Reported as
- 1.04 (0.82-1.31), P = 0.76
- Interval
- 0.82 to 1.31
- Denominator
- Not applicable
- Time window
- Birth
Caveats
Limitations. The trial was powered to detect a relative difference of 35% or more in small-for-gestational-age birth weight, so a smaller increase cannot be ruled out. The percentages come from the 2270 patients with sufficient data (complete-case analysis of the safety outcome); the adjusted risk ratio comes from a multiple-imputation analysis of all 2408 patients (Table 2, N = 2408). Open-label design, one country. The recipient is the newborn, exposed through the mother’s treatment.
Sources and citations (4)
-
Supports Treatment for Mild Chronic Hypertension during Pregnancy
- Locator
- Abstract, RESULTS, sentence 3
- How it applies
- PubMed abstract of the primary report.
- Retrieved
- Source effective date
- Not reported
- Source state
- Current
- Snapshot hash
0d4e3df2a54e7410e41088da17ab93607e2184d8c086a69f5d47053347f746fe- Reuse basis
- Bibliographic metadata and short factual extraction only. The PMC author manuscript states that it is available for text mining and may be used consistent with fair use, so it is not committed and quotations stay at 24 words or fewer. The PubMed abstract carries a publisher copyright notice, so only hashes are kept. The version of record is not redistributed.
-
Supports Treatment for Mild Chronic Hypertension during Pregnancy
- Locator
- Table 2, row Small for gestational age, <10th percentile
- How it applies
- NIH author manuscript (PMC9575330); available for text mining and fair use only; not checked against the version of record. Counts are complete-case; the first ratio is the multiple-imputation adjusted risk ratio.
- Retrieved
- Source effective date
- Not reported
- Source state
- Current
- Snapshot hash
ad310682ed3d8aaac7c162897fc3938d64372fc558622433e3c400aecde53559- Reuse basis
- Bibliographic metadata and short factual extraction only. The PMC author manuscript states that it is available for text mining and may be used consistent with fair use, so it is not committed and quotations stay at 24 words or fewer. The PubMed abstract carries a publisher copyright notice, so only hashes are kept. The version of record is not redistributed.
-
Background Treatment for Mild Chronic Hypertension during Pregnancy
- Locator
- Table 2, column headings and footnotes
- How it applies
- Shows which analysis each column comes from.
- Retrieved
- Source effective date
- Not reported
- Source state
- Current
- Snapshot hash
ad310682ed3d8aaac7c162897fc3938d64372fc558622433e3c400aecde53559- Reuse basis
- Bibliographic metadata and short factual extraction only. The PMC author manuscript states that it is available for text mining and may be used consistent with fair use, so it is not committed and quotations stay at 24 words or fewer. The PubMed abstract carries a publisher copyright notice, so only hashes are kept. The version of record is not redistributed.
-
Background Treatment for Mild Chronic Hypertension during Pregnancy
- Locator
- Methods, Statistical analysis, para 1
- How it applies
- Power of the trial for this outcome.
- Retrieved
- Source effective date
- Not reported
- Source state
- Current
- Snapshot hash
ad310682ed3d8aaac7c162897fc3938d64372fc558622433e3c400aecde53559- Reuse basis
- Bibliographic metadata and short factual extraction only. The PMC author manuscript states that it is available for text mining and may be used consistent with fair use, so it is not committed and quotations stay at 24 words or fewer. The PubMed abstract carries a publisher copyright notice, so only hashes are kept. The version of record is not redistributed.
In plain words
In the CHAP trial, any pre-eclampsia (with or without severe features) occurred in 295 of 1208 women in the treated group (24.4%) and 373 of 1200 women in the control group (31.1%), a risk ratio of 0.79 (95% CI 0.69 to 0.89).
- Pregnant women with known or new chronic hypertension and a viable singleton fetus before 23 weeks of gestation. Mild means below the severe thresholds, but the sources word the limit differently. The abstract says blood pressure below 160/100 mm Hg. The Methods required, at randomization, a systolic pressure of 140 to 159 or a diastolic pressure of 90 to 104 mm Hg for patients who “had not received an antihypertensive drug within 24 hours before measurement”, and below 160 and below 105 mm Hg for patients who “had been receiving antihypertensive therapy”. Women with lower pressures were also eligible. The registry gives a minimum age of 12 years and adds that the minimum age varies by center; the manuscript states no age limit.
- Recruiting sites of the CHAP Trial Consortium in the United States. The Methods say more than 70 recruiting sites; the Results say 2419 women were randomized at 61 sites. The manuscript does not say whether the sites were clinics or hospitals.
- United States
- Pregnancy, enrolled before 23 weeks of gestation and followed until 6 weeks after birth
- Gestational age up to 22 weeks 6 days
- Postnatal age Not reported
Any pre-eclampsia (CHAP definition) Secondary endpoint
295 of 1,208 women in the Active treatment to a goal below 140/90 mm Hg arm
- Measure
- Women with any pre-eclampsia (count)
- Value
- 295 women
- Reported as
- 295 (24.4%)
- Interval
- Not applicable
- Denominator
- n = 1,208
- Time window
- Not stated for this outcome in the manuscript text
373 of 1,200 women in the Standard (control) treatment arm
- Measure
- Women with any pre-eclampsia (count)
- Value
- 373 women
- Reported as
- 373 (31.1%)
- Interval
- Not applicable
- Denominator
- n = 1,200
- Time window
- Not stated for this outcome in the manuscript text
Active treatment to a goal below 140/90 mm Hg compared with Standard (control) treatment
- Measure
- Risk ratio, active treatment vs control (Table 3 treatment effect; the table footnote says it is a risk ratio and the abstract does not call it adjusted)
- Value
- 0.79 ratio
- Reported as
- 0.79 (0.69 to 0.89)
- Interval
- 0.69 to 0.89
- Denominator
- Not applicable
- Time window
- Not stated for this outcome in the manuscript text
Caveats
Limitations. This is a secondary outcome, reported without adjustment for multiplicity, so the authors say it should not be used to infer definitive effects. The risk ratio is not described as adjusted in the abstract or the table. The time window for this outcome is not stated in the manuscript text (follow-up ran to 6 weeks after birth; the primary composite counted pre-eclampsia up to 2 weeks after birth). It overlaps with the severe-features part of the primary composite, so the two must not be added. Open-label design, one country.
Sources and citations (4)
-
Supports Treatment for Mild Chronic Hypertension during Pregnancy
- Locator
- Abstract, RESULTS, sentence 5
- How it applies
- PubMed abstract of the primary report.
- Retrieved
- Source effective date
- Not reported
- Source state
- Current
- Snapshot hash
0d4e3df2a54e7410e41088da17ab93607e2184d8c086a69f5d47053347f746fe- Reuse basis
- Bibliographic metadata and short factual extraction only. The PMC author manuscript states that it is available for text mining and may be used consistent with fair use, so it is not committed and quotations stay at 24 words or fewer. The PubMed abstract carries a publisher copyright notice, so only hashes are kept. The version of record is not redistributed.
-
Supports Treatment for Mild Chronic Hypertension during Pregnancy
- Locator
- Table 3, row Any preeclampsia
- How it applies
- NIH author manuscript (PMC9575330); available for text mining and fair use only; not checked against the version of record.
- Retrieved
- Source effective date
- Not reported
- Source state
- Current
- Snapshot hash
ad310682ed3d8aaac7c162897fc3938d64372fc558622433e3c400aecde53559- Reuse basis
- Bibliographic metadata and short factual extraction only. The PMC author manuscript states that it is available for text mining and may be used consistent with fair use, so it is not committed and quotations stay at 24 words or fewer. The PubMed abstract carries a publisher copyright notice, so only hashes are kept. The version of record is not redistributed.
-
Background Treatment for Mild Chronic Hypertension during Pregnancy
- Locator
- Table 3, column headings and footnote
- How it applies
- Group sizes and the type of treatment effect.
- Retrieved
- Source effective date
- Not reported
- Source state
- Current
- Snapshot hash
ad310682ed3d8aaac7c162897fc3938d64372fc558622433e3c400aecde53559- Reuse basis
- Bibliographic metadata and short factual extraction only. The PMC author manuscript states that it is available for text mining and may be used consistent with fair use, so it is not committed and quotations stay at 24 words or fewer. The PubMed abstract carries a publisher copyright notice, so only hashes are kept. The version of record is not redistributed.
-
Background Treatment for Mild Chronic Hypertension during Pregnancy
- Locator
- Methods, Statistical analysis, para 4
- How it applies
- Secondary outcomes are not adjusted for multiplicity.
- Retrieved
- Source effective date
- Not reported
- Source state
- Current
- Snapshot hash
ad310682ed3d8aaac7c162897fc3938d64372fc558622433e3c400aecde53559- Reuse basis
- Bibliographic metadata and short factual extraction only. The PMC author manuscript states that it is available for text mining and may be used consistent with fair use, so it is not committed and quotations stay at 24 words or fewer. The PubMed abstract carries a publisher copyright notice, so only hashes are kept. The version of record is not redistributed.
Record details
- Record id
maternal:chap-trial- Content hash
55158f7ec3a5ca54f0f81cf6128a216380fe98ed5335083a98cbddfc01626c57