Trial Outcomes & Findings for Clinical Trial of Efficacy and Safety of Ergoferon in the Treatment of Acute Respiratory Viral Infections in Children (NCT NCT03039621)

Last Updated: 2021-08-27

Results Overview

Based on patient diary data. Criteria of alleviation of all ARVI symptoms: oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period) + absence of ARVI symptoms /presence of ARVI symptoms with ≤3-point of the total score (TS) according to the 4-point scale (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom, for each flu-like nonspecific and respiratory symptom). TS ranges from 0 to 30, and the higher scores mean a worse outcome.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

287 participants

Primary outcome timeframe

14 days of observation.

Results posted on

2021-08-27

Participant Flow

Participant milestones

Participant milestones
Measure	Ergoferon 1 tablet 3 times a day. Ergoferon: Inside, orally.	Placebo 1 tablet 3 times a day. Placebo: Inside, orally.
Overall Study STARTED	143	144
Overall Study COMPLETED	131	128
Overall Study NOT COMPLETED	12	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Ergoferon 1 tablet 3 times a day. Ergoferon: Inside, orally.	Placebo 1 tablet 3 times a day. Placebo: Inside, orally.
Overall Study Violation of inclusion criteria	3	2
Overall Study Non-compliance with protocol requirement	4	5
Overall Study Necessity to use drugs forbidden by pro	4	7
Overall Study Violation of non-inclusion criteria	1	2

Baseline Characteristics

ITT sample

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ergoferon n=143 Participants Ergoferon: Tablet for oral use, 1 tablet per intake (outside a meal/feeding). On day 1, five tablets are taken in the first 2 hours (one tablet every 30 min), followed by three more tablets regularly spaced during the rest of the day (total 8 tablets). From day 2, one tablet is taken every 8 hours.	Placebo n=144 Participants Placebo: Placebo using Ergoferon scheme.	Total n=287 Participants Total of all reporting groups
Age, Continuous	3.3 years STANDARD_DEVIATION 1.7 • n=140 Participants • ITT sample	3.4 years STANDARD_DEVIATION 1.7 • n=142 Participants • ITT sample	3.4 years STANDARD_DEVIATION 1.7 • n=282 Participants • ITT sample
Sex: Female, Male Female	73 Participants n=140 Participants • ITT sample	73 Participants n=142 Participants • ITT sample	146 Participants n=282 Participants • ITT sample
Sex: Female, Male Male	67 Participants n=140 Participants • ITT sample	69 Participants n=142 Participants • ITT sample	136 Participants n=282 Participants • ITT sample
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Kazakhstan	26 Participants n=143 Participants	25 Participants n=144 Participants	51 Participants n=287 Participants
Region of Enrollment Russia	117 Participants n=143 Participants	119 Participants n=144 Participants	236 Participants n=287 Participants

PRIMARY outcome

Timeframe: 14 days of observation.

Population: ITT sample

Outcome measures

Outcome measures
Measure	Ergoferon n=140 Participants 1 tablet 3 times a day. Ergoferon: Inside, orally.	Placebo n=142 Participants 1 tablet 3 times a day. Placebo: Inside, orally.
Time to Alleviation of All ARVI Symptoms.	4.5 days Interval 4.2 to 4.8	5.2 days Interval 4.8 to 5.6

SECONDARY outcome

Timeframe: 14 days of observation.

Population: ITT sample

Based on patient diary data. Oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period).

Outcome measures

Outcome measures
Measure	Ergoferon n=140 Participants 1 tablet 3 times a day. Ergoferon: Inside, orally.	Placebo n=142 Participants 1 tablet 3 times a day. Placebo: Inside, orally.
Time to Normalization of Body Temperature.	2.8 days Interval 2.6 to 3.1	3.4 days Interval 3.1 to 3.8

SECONDARY outcome

Timeframe: 14 days of observation.

Population: ITT sample

Based on patient diary data. Absence of flu-like nonspecific symptoms/presence of one mild flu-like nonspecific symptom.

Outcome measures

Outcome measures
Measure	Ergoferon n=140 Participants 1 tablet 3 times a day. Ergoferon: Inside, orally.	Placebo n=142 Participants 1 tablet 3 times a day. Placebo: Inside, orally.
Time to Alleviation of Flu-like Nonspecific Symptoms.	4.0 days Interval 3.7 to 4.3	4.7 days Interval 4.3 to 5.0

SECONDARY outcome

Timeframe: 14 days of observation.

Population: ITT sample

Based on patient diary data. Absence of respiratory symptoms/presence of one mild respiratory symptom.

Outcome measures

Outcome measures
Measure	Ergoferon n=140 Participants 1 tablet 3 times a day. Ergoferon: Inside, orally.	Placebo n=142 Participants 1 tablet 3 times a day. Placebo: Inside, orally.
Time to Alleviation of Respiratory Symptoms.	4.3 days Interval 4.0 to 4.6	5.0 days Interval 4.6 to 5.4

SECONDARY outcome

Timeframe: On days 2-6 of the observation period.

Population: ITT sample

Based on patient diary data. The total score (TS) ranges from 0 to 30 consisting of 4 flu-like nonspecific (decreased activity/weakness, poor appetite/refusal to eat, sick appearance, sleep disturbance) and 6 respiratory (runny nose, stuffy nose/nasal congestion, sneezing, hoarseness, sore throat, cough) symptoms according to the 4-point scale for each symptom (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). TS ranges from 0 to 30, and the higher scores mean a worse outcome.

Outcome measures

Outcome measures
Measure	Ergoferon n=140 Participants 1 tablet 3 times a day. Ergoferon: Inside, orally.	Placebo n=142 Participants 1 tablet 3 times a day. Placebo: Inside, orally.
Flu-like Nonspecific and Respiratory Symptoms Total Score (TS) for Days 2-6. Day 2	12.0 score on a scale Interval 11.2 to 12.9	13.1 score on a scale Interval 12.3 to 13.9
Flu-like Nonspecific and Respiratory Symptoms Total Score (TS) for Days 2-6. Day 3	8.7 score on a scale Interval 7.9 to 9.6	9.7 score on a scale Interval 8.8 to 10.6
Flu-like Nonspecific and Respiratory Symptoms Total Score (TS) for Days 2-6. Day 4	6.2 score on a scale Interval 5.4 to 7.0	7.1 score on a scale Interval 6.2 to 7.9
Flu-like Nonspecific and Respiratory Symptoms Total Score (TS) for Days 2-6. Day 5	3.9 score on a scale Interval 3.3 to 4.5	5.1 score on a scale Interval 4.4 to 5.9
Flu-like Nonspecific and Respiratory Symptoms Total Score (TS) for Days 2-6. Day 6	2.5 score on a scale Interval 2.1 to 3.0	3.7 score on a scale Interval 3.1 to 4.4

SECONDARY outcome

Timeframe: On days 2-6 of the observation period.

Population: ITT sample

Based on the area under the curve of TS for days 2-6, according to the patient diary. The total score (TS) will be calculated based on the severity of each ARVI symptom (sum of 11 symptoms = body temperature, flu-like nonspecific symptoms (4 symptoms) and respiratory symptoms (6 symptoms) according to the 4-point scale (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To calculate TS the absolute oral temperature values, measured in degrees Celsius, will be converted into relative units (or points), given the following gradations: ≤37.5С = 0 point; 37.6-38.1C = 1 point; 38.2-38.8C = 2 points; ≥38.90С = 3 points. For total score minimum and maximum scores are 0 and 33, where higher values represent a worse outcome.

Outcome measures

Outcome measures
Measure	Ergoferon n=140 Participants 1 tablet 3 times a day. Ergoferon: Inside, orally.	Placebo n=142 Participants 1 tablet 3 times a day. Placebo: Inside, orally.
ARVI Severity.	39.6 score on a scale*day Interval 36.4 to 42.8	44.6 score on a scale*day Interval 41.2 to 48.1

SECONDARY outcome

Timeframe: On days 2-6 of the observation period.

Population: ITT sample

Based on patient diary data. Criteria of recovery/alleviation of all ARVI symptoms: oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period) + absence of ARVI symptoms /presence of ARVI symptoms with ≤3-point of the total score (TS) according to the 4-point scale for each flu-like nonspecific and respiratory symptom (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom, for each flu-like nonspecific and respiratory symptom).

Outcome measures

Outcome measures
Measure	Ergoferon n=140 Participants 1 tablet 3 times a day. Ergoferon: Inside, orally.	Placebo n=142 Participants 1 tablet 3 times a day. Placebo: Inside, orally.
Percentage of Recovered Patients. Day 2	20 Participants	20 Participants
Percentage of Recovered Patients. Day 3	37 Participants	35 Participants
Percentage of Recovered Patients. Day 4	72 Participants	61 Participants
Percentage of Recovered Patients. Day 5	102 Participants	91 Participants
Percentage of Recovered Patients. Day 6	119 Participants	98 Participants

SECONDARY outcome

Timeframe: On days 1- 5 of the treatment period.

Population: ITT sample

Based on patient diary data. The number of intakes of prescribed antipyretics.

Outcome measures

Outcome measures
Measure	Ergoferon n=140 Participants 1 tablet 3 times a day. Ergoferon: Inside, orally.	Placebo n=142 Participants 1 tablet 3 times a day. Placebo: Inside, orally.
Rates of Antipyretics Use Per Patient. Day 1	1.5 number per patient Interval 1.3 to 1.6	1.6 number per patient Interval 1.4 to 1.7
Rates of Antipyretics Use Per Patient. Day 2	1.0 number per patient Interval 0.9 to 1.2	1.2 number per patient Interval 1.0 to 1.4
Rates of Antipyretics Use Per Patient. Day 3	0.4 number per patient Interval 0.2 to 0.5	0.5 number per patient Interval 0.4 to 0.6
Rates of Antipyretics Use Per Patient. Day 4	0.2 number per patient Interval 0.1 to 0.2	0.2 number per patient Interval 0.1 to 0.3
Rates of Antipyretics Use Per Patient. Day 5	0.0 number per patient Interval 0.0 to 0.1	0.1 number per patient Interval 0.0 to 0.2

SECONDARY outcome

Timeframe: 14 days of observation peiod.

Population: ITT sample

Based on patient diary data. The disease worsening: ARVI complications, including those requiring antibiotics; hospitalization).

Outcome measures

Outcome measures
Measure	Ergoferon n=140 Participants 1 tablet 3 times a day. Ergoferon: Inside, orally.	Placebo n=142 Participants 1 tablet 3 times a day. Placebo: Inside, orally.
Percentage of Patients With Worsening of Illness.	1 Participants	19 Participants

Adverse Events

Ergoferon

Serious events: 0 serious events

Other events: 10 other events

Deaths: 10 deaths

Placebo

Serious events: 0 serious events

Other events: 27 other events

Deaths: 27 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Michael Putilovskiy, MD, PhD, Clinical and Medical Department Director

Materia Medica Holding

Phone: +74952761571

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Ergoferon n=143 participants at risk 1 tablet 3 times a day. Ergoferon: Inside, orally.	Placebo n=144 participants at risk 1 tablet 3 times a day. Placebo: Inside, orally.
Skin and subcutaneous tissue disorders Urticaria	0.70% 1/143 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.00% 0/144 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Skin and subcutaneous tissue disorders Exfoliative rash	0.70% 1/143 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.00% 0/144 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Blood and lymphatic system disorders Lymphadenitis	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Cardiac disorders Tachycardia	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Eye disorders Eyelid oedema	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Gastrointestinal disorders Diarrhoea	1.4% 2/143 • Number of events 2 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 2 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Gastrointestinal disorders Vomiting	0.70% 1/143 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Gastrointestinal disorders Teething	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Gastrointestinal disorders Abdominal pain	0.70% 1/143 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.00% 0/144 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
General disorders Hyperthermia	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
General disorders Condition worsened	0.70% 1/143 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	2.1% 3/144 • Number of events 3 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Infections and infestations Adenoiditis	0.70% 1/143 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	5.6% 8/144 • Number of events 8 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Infections and infestations Bronchitis	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	2.8% 4/144 • Number of events 4 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Infections and infestations Gastroenteritis	0.70% 1/143 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.00% 0/144 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Infections and infestations Tracheitis	0.70% 1/143 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.00% 0/144 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Infections and infestations Otitis media acute	0.70% 1/143 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	1.4% 2/144 • Number of events 2 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Infections and infestations Rhinitis	0.70% 1/143 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.00% 0/144 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Infections and infestations Adenoviral upper respiratory infection	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Infections and infestations Gastroenterocolitis	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Infections and infestations Oral herpes	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Infections and infestations Infectious mononucleosis	0.70% 1/143 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.00% 0/144 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Infections and infestations Pharyngotonsillitis	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	1.4% 2/144 • Number of events 2 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Injury, poisoning and procedural complications Procedural vomiting	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Musculoskeletal and connective tissue disorders Muscle twitching	0.70% 1/143 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.00% 0/144 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Musculoskeletal and connective tissue disorders Torticollis	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	1.4% 2/144 • Number of events 2 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).
Skin and subcutaneous tissue disorders Rash	0.00% 0/143 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).	0.69% 1/144 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods). Adverse/Serious adverse events were registered in patients of the Safety population (n=287).