Acute Respiratory Distress SyndromeR2NCT04695392

Restore Resilience in Critically Ill Children

A study testing R2 Bundle in people with Acute Respiratory Distress Syndrome, run by University of Pennsylvania at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The study design will allow investigators to describe usual care in each PICU and identify the facilitating and restraining factors impacting the implementation of R2 at each PICU. The purpose of this pilot study is to improve the care, environment, daily routine and sleep patterns of children in the PICU. Read more about this study

Who is it for?: Ages 6 months to 17 years
Conditions the study is for: Acute Respiratory Distress Syndrome
What is being tested?: R2 Bundle
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 56 participants
Where: 2 sitesUnited States
Study dates: 5 Sep 2017to 31 Dec 2021
Phase: Interventional
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 6 months to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

PICU admission at one of the study sites in which elements of R2 are typically but sporadically implemented
Transferred to the PICU from another hospital unit/ward with ≤4 nights in the hospital (≤2 nights in PICU)
Between the ages 6 months and 18 years at the time of enrollment (has not had their 18th birthday)
Intubated and mechanically ventilated for acute airway or parenchymal disease within last 48 hours
Expected to be intubated for more than 12 hours past enrollment
Parent/Guardian providing consent, provides primary care for subject

Who cannot join

A baseline cognitive dysfunction, measured by the Pediatric Cerebral Performance Category (PCPC ≥4)
A history of an uncontrolled seizure disorder (seizure within past 3 months), cerebral hypertension, neuromuscular respiratory failure, ventilator dependence (excluding BiPAP or CPAP at night)
A history of inability to tolerate bolus enteral feeds (full J-Tube fed patients)
The presence of any of the following within 24 hours of admission:
Modal pain scores greater than 4
Persistent hypotension/hypertension unresponsive to standard therapies

Show all 9Show fewer

Use of High Frequency Oscillatory Ventilation or Extracorporeal Membrane Oxygenation
Administered melatonin within the past week
Has an active do-not-resuscitate plan

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Johns Hopkins University - Charlotte Bloomberg Children's Center
Baltimore, Maryland, 21287
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Read the detailed description

Hospitals should do the sick no harm. That noted, modern day pediatric intensive care units (PICUs) are not healing milieus. Immediately upon admission to the PICU, the child's daily routine and sleep patterns are replaced by a well-intended but not patient-centered PICU routine. The interprofessional investigative team believes that PICU care and environments can be modulated to sustain a young child's circadian rhythm (CR) and support their physiological resilience and capacity to heal. The first step in this program of research is to pilot-test RESTORE resilience (R2), a 7-item individualized bundle that we hypothesize will restore CR in critically ill children using a pre-posttest design. Two separate PICUs will each enroll 10 baseline subjects followed by 20 intervention subjects, 6 months to 18 years of age, who are intubated and mechanically ventilated for acute respiratory failure. Specifically, as soon as possible after PICU admission, parents will be interviewed to create an individualized chronotherapeutic bundle to include (1) focused effort to replicate the child's pre-hospitalization daily routine (bedtime/wake time, bedtime/arousal routine, nap time, feeding schedule, active periods), (2) cycled day-night lighting and modulation of sound to match the child's routine, (3) minimal yet effective sedation using a nurse-implemented goal-directed sedation plan (RESTORE), (4) night fasting with bolus enteral daytime feedings, (5) early, developmentally-appropriate, progressive exercise and mobility (PICU Up!), (6) continuity in nursing care, and (7) parent diaries. The overall objective of this study is to pilot-test an intervention that can be implemented in any PICU that will improve sleep-wake patterns with restoration/maintenance of circadian rhythms in critically ill children with acute respiratory failure. Results of this pilot study will be used to inform the design of an adequately powered multicenter randomized trial of R2.

Conditions: Acute Respiratory Distress Syndrome
Being tested: R2 Bundle
Medical subject headings: Respiratory Distress Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

R2 BundleOther
During the intervention phase subjects will receive R2.
1. Focused effort to replicate the child's pre-hospitalization daily routine (bedtime/wake time, bedtime/arousal routine, nap time, feeding schedule, active periods),
2. Cycled day-night lighting and modulation of sound to match the child's routine,
3. Minimal yet effective sedation using a nurse-implemented goal-directed sedation plan (RESTORE),
4. Night fasting with bolus enteral daytime feedings,
5. Early, developmentally-appropriate, progressive exercise and mobility (PICU Up!),
6. Continuity in nursing care, and
7. Parent diaries.

Study groups in NCT04695392
Study group	Role	What they receive
Intervention	Experimental	R2 Bundle Receives: Other: R2 Bundle
Baseline	No intervention	Usual care

What is being measured

The primary outcome is the main question the study is designed to answer.

DARE (Daytime Activity Ratio Estimate), Post Extubation
DARE = Daytime Activity Ratio Estimate after endotracheal extubation; DARE was calculated by dividing daytime (07:00-18:59) activity count by 24-hour activity count. A DARE of 50% indicates equal amount of activity between daytime and nighttime periods (loss of circadian rhythm), while a higher DARE indicates increased daytime activity and nighttime sleep consolidation.
Measured: From immediately after endotracheal extubation to PICU discharge, assessed for up to 28 days

Secondary outcomes (14)

Delta Between Average Nighttime and Average Daytime Salivary Melatonin Levels
Delta between average nighttime (19:00 to 06:59) and average daytime (07:00 to 18:59) salivary melatonin levels
Measured: Day 5 of PICU hospitalization
Percentage of Study Days Where Light and Sound Were Modulated
Percentage of study days where light and sound were modulated to reflect day-night variation in light and sound levels; 0 = no study days where light and sound were modulated; 100% = light and sound modulated on all study days
Measured: From date of enrollment until the date of PICU discharge, assessed for up to 28 days
Percentage of Study Days Where the Patient Not Fed Enterally After Bedtime
Percentage of study days where the patient was not fed enterally after bedtime
Measured: From date of enrollment until the date of PICU discharge, assessed for up to 28 days
Continuity in Nursing Care
Continuity in Nursing Care Index (CINC) defined as (N nurses/N shifts)*100. Score range 0-100, lower scores are better.
Measured: From date of enrollment until the date of PICU discharge, assessed for up to 28 days
Pain Free Days
Percentage of PICU days where pain was assessed (0-10 pain scale) without pain (Pain score <4)
Measured: From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Agitation Free Days
Percentage of PICU days without agitation (Agitation = State Behavioral Scale [SBS; range -3 to +2] >/= 1)
Measured: From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Delirium Free Days
Percentage of PICU days, where delirium was assessed, without delirium (using the CAPD, pCAM-ICU or psCAM-ICU; cut score determined by instrument)
Measured: From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Iatrogenic Withdrawal Syndrome (IWS) Free Days
Percentage of PICU days without IWS (Withdrawal Assessment Tool - version 1 [WAT-1]; range of scores 0-12 where no IWS = WAT-1 < 3)
Measured: From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Peak Daily Dose of All Opioid Sedative Agents
Highest daily mg/kg dose of all opioid sedative agents
Measured: From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Cumulative Dose of All Opioid Sedative Agents
Total PICU mg/kg dose of all opioid sedative agents received
Measured: From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Total PICU Days of Opioid Sedation
Total number of PICU days exposed to opioid sedation
Measured: From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
PICU Length of Stay
Time between the start and stop of PICU care
Measured: From date and time of PICU admission until the date and time of PICU discharge
Parent Perception of Being well-cared-for
Percent match on the 7-item family-centered care scale (FCCS); range from 0-100% match; where higher scores indicate a better match
Measured: On the date of PICU discharge, assessed once within an average of 2 weeks post PICU admission
DARE (Daytime Activity Ratio Estimate), Acute Phase
DARE = Daytime Activity Ratio Estimate after endotracheal extubation; DARE was calculated by dividing daytime (07:00-18:59) activity count by 24-hour activity count. A DARE of 50% indicates equal amount of activity between daytime and nighttime periods (loss of circadian rhythm), while a higher DARE indicates increased daytime activity and nighttime sleep consolidation.
Measured: From study enrollment to endotracheal extubation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Sep 201731 Dec 2021

First posted5 Jan 2021
Study start5 Sep 2017
Primary completion31 Dec 2021
Study completion31 Dec 2021

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.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
More trials run by University of PennsylvaniaThe 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 N/A
Primary purpose: Supportive care
Allocation: Non-randomised
Intervention model: Parallel groups
Model description: Pre-post study
Masking: None (open label)
Enrolment: 56 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04695392
Sponsor's protocol ID: 828061
Acronym: R2
Status last verified: Apr 2024
First submitted: 22 Dec 2020
Last updated: 11 May 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Perry MA, Dawkins-Henry OS, Awojoodu RE, Blumenthal J, Asaro LA, Wypij D, Kudchadkar SR, Zuppa AF, Curley MAQ. Study protocol for a two-center test of a nurse-implemented chronotherapeutic restoring bundle in critically ill children: RESTORE Resilience (R2). Contemp Clin Trials Commun. 2021 Aug 19;23:100840. doi: 10.1016/j.conctc.2021.100840. eCollection 2021 Sep.
PubMed 34466711
Curley MAQ, Dawkins-Henry OS, Kalvas LB, Perry-Eaddy MA, Georgostathi G, Yuan I, Wypij D, Asaro LA, Zuppa AF, Kudchadkar SR. The Nurse-Implemented Chronotherapeutic Bundle in Critically Ill Children, RESTORE Resilience (R 2 ): Pilot Testing in a Two-Phase Cohort Study, 2017-2021. Pediatr Crit Care Med. 2024 Nov 1;25(11):1051-1064. doi: 10.1097/PCC.0000000000003595. Epub 2024 Aug 12.
PubMed 39133067
Kalvas LB, Dawkins-Henry OS, Ordway MR, Kudchadkar SR, Asaro LA, Wypij D, Curley MAQ. Sleep Health in Critically Ill Children With Acute Respiratory Failure. AACN Adv Crit Care. 2026 Mar 15;37(1):107-121. doi: 10.4037/aacnacc2026606.
PubMed 41758709

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Acute Respiratory Distress Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Restore Resilience in Critically Ill Children
ClinicalTrials.gov ID: NCT04695392
Acronym / sponsor ID: R2 / 828061
Conditions: Acute Respiratory Distress Syndrome
Study type: Interventional
Recruitment status: Completed
Enrolment: 56 participants (actual)
Lead sponsor: University of PennsylvaniaUniversity, hospital or other
Collaborators: Johns Hopkins University, Children's Hospital of Philadelphia, Boston Children's Hospital
Study start: 5 Sep 2017 (actual)
Primary completion: 31 Dec 2021 (actual)
Study completion: 31 Dec 2021 (actual)
First posted: 5 Jan 2021 (actual)
Results: Posted 30 Apr 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Supportive care
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: Pre-post study

Arm	Type	Receives
Intervention	Experimental	Other: R2 BundleR2 Bundle
Baseline	No intervention	–Usual care

Who may qualify

Ages: 6 months to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (6 listed)

PICU admission at one of the study sites in which elements of R2 are typically but sporadically implemented
Transferred to the PICU from another hospital unit/ward with ≤4 nights in the hospital (≤2 nights in PICU)
Between the ages 6 months and 18 years at the time of enrollment (has not had their 18th birthday)
Intubated and mechanically ventilated for acute airway or parenchymal disease within last 48 hours
Expected to be intubated for more than 12 hours past enrollment

Key exclusion criteria (9 listed)

A baseline cognitive dysfunction, measured by the Pediatric Cerebral Performance Category (PCPC ≥4)
A history of an uncontrolled seizure disorder (seizure within past 3 months), cerebral hypertension, neuromuscular respiratory failure, ventilator dependence (excluding BiPAP or CPAP at night)
A history of inability to tolerate bolus enteral feeds (full J-Tube fed patients)
The presence of any of the following within 24 hours of admission:
Administered melatonin within the past week

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
R2 BundleDuring the intervention phase subjects will receive R2. 1. Focused effort to replicate the child's pre-hospitalization daily routine (bedtime/wake time, bedtime/arousal routine, nap time, feeding schedule, active periods), 2. Cycled day-night lighting and modulation of sound to match the child's routine, 3. Minimal yet effective sedation using a nurse-implemented goal-directed sedation plan (RESTORE), 4. Night fasting with bolus enteral daytime feedings, 5. Early, developmentally-appropriate, progressive exercise and mobility (PICU Up!), 6. Continuity in nursing care, and 7. Parent diaries.	Other	Intervention

Primary outcome

DARE (Daytime Activity Ratio Estimate), Post Extubation
Time frame: From immediately after endotracheal extubation to PICU discharge, assessed for up to 28 days
DARE = Daytime Activity Ratio Estimate after endotracheal extubation; DARE was calculated by dividing daytime (07:00-18:59) activity count by 24-hour activity count. A DARE of 50% indicates equal amount of activity between daytime and nighttime periods (loss of circadian rhythm), while a higher DARE indicates increased daytime activity and nighttime sleep consolidation.

14 secondary outcomes

Delta Between Average Nighttime and Average Daytime Salivary Melatonin Levels
Time frame: Day 5 of PICU hospitalization
Percentage of Study Days Where Light and Sound Were Modulated
Time frame: From date of enrollment until the date of PICU discharge, assessed for up to 28 days
Percentage of Study Days Where the Patient Not Fed Enterally After Bedtime
Time frame: From date of enrollment until the date of PICU discharge, assessed for up to 28 days
Continuity in Nursing Care
Time frame: From date of enrollment until the date of PICU discharge, assessed for up to 28 days
Pain Free Days
Time frame: From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Agitation Free Days
Time frame: From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Delirium Free Days
Time frame: From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Iatrogenic Withdrawal Syndrome (IWS) Free Days
Time frame: From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Peak Daily Dose of All Opioid Sedative Agents
Time frame: From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Cumulative Dose of All Opioid Sedative Agents
Time frame: From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Total PICU Days of Opioid Sedation
Time frame: From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
PICU Length of Stay
Time frame: From date and time of PICU admission until the date and time of PICU discharge
Parent Perception of Being well-cared-for
Time frame: On the date of PICU discharge, assessed once within an average of 2 weeks post PICU admission
DARE (Daytime Activity Ratio Estimate), Acute Phase
Time frame: From study enrollment to endotracheal extubation

Results and safety

Results posted to the registry on 30 Apr 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Baseline	20	20
Intervention	36	34

Primary outcome: DARE (Daytime Activity Ratio Estimate), Post Extubation

Time frame: From immediately after endotracheal extubation to PICU discharge, assessed for up to 28 days. Median (Inter-Quartile Range). Unit: Percentage of total activity

Measure	Baseline n = 18	Intervention n = 32
Value	56.7 (47.6 to 65.5)	61.7 (52.7 to 64.8)

Population analysed: Primary outcome not available for 4 subjects.

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: From date of enrollment until the date of PICU discharge, assessed for up to 28 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Baseline	0 of 20 (0%)	1 of 20 (5%)	0 of 20
Intervention	0 of 34 (0%)	1 of 34 (2.9%)	0 of 34

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 34466711Perry MA, Dawkins-Henry OS, Awojoodu RE, Blumenthal J, Asaro LA, Wypij D, Kudchadkar SR, Zuppa AF, Curley MAQ. Study protocol for a two-center test of a nurse-implemented chronotherapeutic restoring bundle in critically ill children: RESTORE Resilience (R2). Contemp Clin Trials Commun. 2021 Aug 19;23:100840. doi: 10.1016/j.conctc.2021.100840. eCollection 2021 Sep.
Results publication: PubMed 39133067Curley MAQ, Dawkins-Henry OS, Kalvas LB, Perry-Eaddy MA, Georgostathi G, Yuan I, Wypij D, Asaro LA, Zuppa AF, Kudchadkar SR. The Nurse-Implemented Chronotherapeutic Bundle in Critically Ill Children, RESTORE Resilience (R 2 ): Pilot Testing in a Two-Phase Cohort Study, 2017-2021. Pediatr Crit Care Med. 2024 Nov 1;25(11):1051-1064. doi: 10.1097/PCC.0000000000003595. Epub 2024 Aug 12.
Derived from this study: PubMed 41758709Kalvas LB, Dawkins-Henry OS, Ordway MR, Kudchadkar SR, Asaro LA, Wypij D, Curley MAQ. Sleep Health in Critically Ill Children With Acute Respiratory Failure. AACN Adv Crit Care. 2026 Mar 15;37(1):107-121. doi: 10.4037/aacnacc2026606.
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.

Martha AQ Curley, RN, PhD principal investigator

University of Pennsylvania

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing R2 Bundle in people with Acute Respiratory Distress Syndrome, run by University of Pennsylvania at 2 sites 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 6 inclusion and 9 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 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Apr 2024). 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?

DARE (Daytime Activity Ratio Estimate), Post Extubation (time frame: From immediately after endotracheal extubation to PICU discharge, assessed for up to 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04695392, which also lists 3 linked publications.

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 11 May 2026.