Trial Outcomes & Findings for Impact of Discontinuing Hypertonic Saline in People With CF on Highly Effective CFTR Modulators- A SIMPLIFY Sub-Study (NCT NCT06350461)

Last Updated: 2024-10-01

Results Overview

Difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week 0 to Week 6.

Recruitment status

COMPLETED

Study phase

Target enrollment

370 participants

Primary outcome timeframe

Week 0 to Week 6

Results posted on

2024-10-01

Participant Flow

Participant milestones

Participant milestones
Measure	HS-Discontinue Discontinuation of current hypertonic saline (HS) therapy Discontinuation of hypertonic saline (HS): Discontinuation of current hypertonic saline (HS) therapy during 6-week study period.	HS-Continue Continuation of current hypertonic saline (HS) therapy Continuation of hypertonic saline (HS): Continuation of current hypertonic saline (HS) therapy during 6-week study period. Therapy is taken at least once daily according to each participant's pre-existing, clinically prescribed regimen (e.g., daily, twice daily). The concentration of HS is according to clinical prescription (e.g., 7% sodium chloride or 3.5% sodium chloride) and at least 3%.
Overall Study STARTED	184	186
Overall Study COMPLETED	181	183
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Impact of Discontinuing Hypertonic Saline in People With CF on Highly Effective CFTR Modulators- A SIMPLIFY Sub-Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HS-Discontinue n=133 Participants Discontinuation of current hypertonic saline (HS) therapy Discontinuation of hypertonic saline (HS): Discontinuation of current hypertonic saline (HS) therapy during 6-week study period.	HS-Continue n=140 Participants Continuation of current hypertonic saline (HS) therapy Continuation of hypertonic saline (HS): Continuation of current hypertonic saline (HS) therapy during 6-week study period. Therapy is taken at least once daily according to each participant's pre-existing, clinically prescribed regimen (e.g., daily, twice daily). The concentration of HS is according to clinical prescription (e.g., 7% sodium chloride or 3.5% sodium chloride) and at least 3%.	Total n=273 Participants Total of all reporting groups
Age, Continuous	21.8 years STANDARD_DEVIATION 11.06 • n=5 Participants	23.5 years STANDARD_DEVIATION 11.34 • n=7 Participants	22.7 years STANDARD_DEVIATION 11.22 • n=5 Participants
Age, Customized Age Distribution (years) · >=12 to 18	68 Participants n=5 Participants	64 Participants n=7 Participants	132 Participants n=5 Participants
Age, Customized Age Distribution (years) · >=18 to <24	24 Participants n=5 Participants	28 Participants n=7 Participants	52 Participants n=5 Participants
Age, Customized Age Distribution (years) · >=24 to <30	22 Participants n=5 Participants	15 Participants n=7 Participants	37 Participants n=5 Participants
Age, Customized Age Distribution (years) · >=30	19 Participants n=5 Participants	33 Participants n=7 Participants	52 Participants n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	63 Participants n=7 Participants	128 Participants n=5 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	77 Participants n=7 Participants	145 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants	6 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	122 Participants n=5 Participants	134 Participants n=7 Participants	256 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	128 Participants n=5 Participants	136 Participants n=7 Participants	264 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaskan Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other, More than one Race, or Unknown/Not Reported	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Cystic Fibrosis (CF) Genotype F508 Homozygous	82 Participants n=5 Participants	84 Participants n=7 Participants	166 Participants n=5 Participants
Cystic Fibrosis (CF) Genotype F508 Heterozygous	51 Participants n=5 Participants	53 Participants n=7 Participants	104 Participants n=5 Participants
Cystic Fibrosis (CF) Genotype Other or Unknown	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Forced Expiratory Volume in 1 second (FEV1)	3.4 Liters STANDARD_DEVIATION 0.91 • n=5 Participants	3.4 Liters STANDARD_DEVIATION 0.89 • n=7 Participants	3.4 Liters STANDARD_DEVIATION 0.90 • n=5 Participants
FEV1 (% Predicted) Distribution <60	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
FEV1 (% Predicted) Distribution >=60 to <70	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
FEV1 (% Predicted) Distribution >=70 to <90	32 Participants n=5 Participants	37 Participants n=7 Participants	69 Participants n=5 Participants
FEV1 (% Predicted) Distribution >=90 to <100	31 Participants n=5 Participants	26 Participants n=7 Participants	57 Participants n=5 Participants
FEV1 (% Predicted) Distribution >=100	60 Participants n=5 Participants	66 Participants n=7 Participants	126 Participants n=5 Participants
FEV1 (% Predicted)	97.6 Percent of Predicted STANDARD_DEVIATION 17.55 • n=5 Participants	96.8 Percent of Predicted STANDARD_DEVIATION 17.30 • n=7 Participants	97.2 Percent of Predicted STANDARD_DEVIATION 17.40 • n=5 Participants
Current Dornase Alfa Use	111 Participants n=5 Participants	120 Participants n=7 Participants	231 Participants n=5 Participants
Current Airway Clearance Use	127 Participants n=5 Participants	132 Participants n=7 Participants	259 Participants n=5 Participants
Previous Enrollment in SIMPLIFY-DA Study Yes	42 Participants n=5 Participants	45 Participants n=7 Participants	87 Participants n=5 Participants
Previous Enrollment in SIMPLIFY-DA Study No	91 Participants n=5 Participants	95 Participants n=7 Participants	186 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 0 to Week 6

Population: Per Protocol Population

Difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week 0 to Week 6.

Outcome measures

Outcome measures
Measure	HS-Discontinue n=133 Participants Discontinuation of current hypertonic saline (HS) therapy Discontinuation of hypertonic saline (HS): Discontinuation of current hypertonic saline (HS) therapy during 6-week study period.	HS-Continue n=140 Participants Continuation of current hypertonic saline (HS) therapy Continuation of hypertonic saline (HS): Continuation of current hypertonic saline (HS) therapy during 6-week study period. Therapy is taken at least once daily according to each participant's pre-existing, clinically prescribed regimen (e.g., daily, twice daily). The concentration of HS is according to clinical prescription (e.g., 7% sodium chloride or 3.5% sodium chloride) and at least 3%.
Absolute Change in FEV1 % Predicted From Week 0 to Week 6	-0.2 FEV1 % predicted Standard Deviation 4.10	0.1 FEV1 % predicted Standard Deviation 3.64

SECONDARY outcome

Timeframe: Baseline (Week 0 or Week -2) to Week 6

Population: Participants in the per-protocol (PP) population with an acceptable LCI 2.5 measurement at baseline and at Week 6.

Difference between study arms (discontinue - continue) in the absolute change in LCI 2.5 (Lung Clearance Index) from Baseline (Week 0, if available, or else Week -2) to Week 6. LCI 2.5 is the number of times the volume in the lungs needs to turn over to expel an inert gas. A higher value of LCI 2.5 indicates poorer lung function.

Outcome measures

Outcome measures
Measure	HS-Discontinue n=31 Participants Discontinuation of current hypertonic saline (HS) therapy Discontinuation of hypertonic saline (HS): Discontinuation of current hypertonic saline (HS) therapy during 6-week study period.	HS-Continue n=28 Participants Continuation of current hypertonic saline (HS) therapy Continuation of hypertonic saline (HS): Continuation of current hypertonic saline (HS) therapy during 6-week study period. Therapy is taken at least once daily according to each participant's pre-existing, clinically prescribed regimen (e.g., daily, twice daily). The concentration of HS is according to clinical prescription (e.g., 7% sodium chloride or 3.5% sodium chloride) and at least 3%.
Absolute Change in LCI 2.5 From Baseline to Week 6	0.1 number of lung volume turnovers Standard Deviation 0.72	0.1 number of lung volume turnovers Standard Deviation 0.73

SECONDARY outcome

Timeframe: Week 0 to Week 6

Population: Participants in the per-protocol (PP) population with a CRISS score at Week 0 and Week 6

Difference between study arms (discontinue - continue) in the absolute change in respiratory symptoms, as measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) from Week 0 to Week 6. The Cystic Fibrosis Respiratory Symptoms Daily Diary (CFRSD) asks a participant to state the extent of their 8 respiratory symptoms: difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present 'a great deal' or 'extremely'. A summed score (range from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where the lowest scores indicate improvement of symptoms. Calculation of a score requires responses for at least 7 out of 8 symptoms.

Outcome measures

Outcome measures
Measure	HS-Discontinue n=132 Participants Discontinuation of current hypertonic saline (HS) therapy Discontinuation of hypertonic saline (HS): Discontinuation of current hypertonic saline (HS) therapy during 6-week study period.	HS-Continue n=140 Participants Continuation of current hypertonic saline (HS) therapy Continuation of hypertonic saline (HS): Continuation of current hypertonic saline (HS) therapy during 6-week study period. Therapy is taken at least once daily according to each participant's pre-existing, clinically prescribed regimen (e.g., daily, twice daily). The concentration of HS is according to clinical prescription (e.g., 7% sodium chloride or 3.5% sodium chloride) and at least 3%.
Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) From Week 0 to Week 6	-1.4 score on a scale Standard Deviation 11.02	0.2 score on a scale Standard Deviation 9.73

SECONDARY outcome

Timeframe: Week 0 to Week 6

Population: Participants in the per-protocol (PP) population with a score at Week 0 and at Week 6

Difference between study arms (discontinue - continue) in the absolute change in respiratory symptoms, as measured by the Cystic Fibrosis Questionnaire-Revised Respiratory Domain Score from Week 0 to Week 6. The Cystic Fibrosis Questionnaire - Revised asks participants 6 questions related to respiratory symptoms which are each assigned a score 1-4. The Respiratory Domain Scaled Score is calculated as follows: 100\*\[{sum of responses}/{number of responses}-1\]/3 only if number of responses ≥ 3; otherwise the score is set to missing. The scaled score ranges from 0 to 100 where higher scores indicate improvement of symptoms.

Outcome measures

Outcome measures
Measure	HS-Discontinue n=133 Participants Discontinuation of current hypertonic saline (HS) therapy Discontinuation of hypertonic saline (HS): Discontinuation of current hypertonic saline (HS) therapy during 6-week study period.	HS-Continue n=140 Participants Continuation of current hypertonic saline (HS) therapy Continuation of hypertonic saline (HS): Continuation of current hypertonic saline (HS) therapy during 6-week study period. Therapy is taken at least once daily according to each participant's pre-existing, clinically prescribed regimen (e.g., daily, twice daily). The concentration of HS is according to clinical prescription (e.g., 7% sodium chloride or 3.5% sodium chloride) and at least 3%.
Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain From Week 0 to Week 6	0.7 score on a scale Standard Deviation 9.56	0.5 score on a scale Standard Deviation 6.35

SECONDARY outcome

Timeframe: Week -2 to Week 0

Population: Per-protocol (PP) population

Difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week -2 to Week 0.

Outcome measures

Outcome measures
Measure	HS-Discontinue n=133 Participants Discontinuation of current hypertonic saline (HS) therapy Discontinuation of hypertonic saline (HS): Discontinuation of current hypertonic saline (HS) therapy during 6-week study period.	HS-Continue n=140 Participants Continuation of current hypertonic saline (HS) therapy Continuation of hypertonic saline (HS): Continuation of current hypertonic saline (HS) therapy during 6-week study period. Therapy is taken at least once daily according to each participant's pre-existing, clinically prescribed regimen (e.g., daily, twice daily). The concentration of HS is according to clinical prescription (e.g., 7% sodium chloride or 3.5% sodium chloride) and at least 3%.
Absolute Change in FEV1 % Predicted From Week -2 to Week 0	0.2 % predicted Standard Deviation 3.63	-0.4 % predicted Standard Deviation 3.86

SECONDARY outcome

Timeframe: Week 0 to Week 2

Population: Participants in the per-protocol (PP) population with FEV1 measurements at Week 0 and at Week 2

Difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week 0 to Week 2.

Outcome measures

Outcome measures
Measure	HS-Discontinue n=128 Participants Discontinuation of current hypertonic saline (HS) therapy Discontinuation of hypertonic saline (HS): Discontinuation of current hypertonic saline (HS) therapy during 6-week study period.	HS-Continue n=138 Participants Continuation of current hypertonic saline (HS) therapy Continuation of hypertonic saline (HS): Continuation of current hypertonic saline (HS) therapy during 6-week study period. Therapy is taken at least once daily according to each participant's pre-existing, clinically prescribed regimen (e.g., daily, twice daily). The concentration of HS is according to clinical prescription (e.g., 7% sodium chloride or 3.5% sodium chloride) and at least 3%.
Absolute Change in FEV1 % Predicted From Week 0 to Week 2	0.3 % predicted Standard Deviation 3.66	0.6 % predicted Standard Deviation 2.94

SECONDARY outcome

Timeframe: Week 0 to Week 6

Population: Intent to treat (ITT) population of all randomized participants

Difference between study arms (discontinue - continue) in the percent of subjects initiating acute oral, inhaled or intravenous antibiotics from Week 0 to Week 6. Includes antibiotics initiated for respiratory indications; excludes those taken as part of a chronic cycled regimen or for a UTI, skin infection, etc.