Pilot and main RCT design
The pilot study of 10 participants and the subsequent large-scale trial used an identical randomized controlled design and procedures. Study participants were hospital patients who had experienced a potentially traumatic event within the last 72 hours. Participants were allocated to either modified PE or a control condition. The sample reported throughout this paper is the pooled sample of 10 participants from the pilot study and the first 22 from the RCT.
Eligible participants were Swedish-speaking patients over 16 years of age attending the emergency department (ED) at Karolinska University hospital in Solna, Sweden, within 72 hours after experiencing a psychologically traumatic event according to the DSM-5 criterion A for PTSD (i.e., exposed to: death, threatened death, actual or threatened serious injury, or actual or threatened sexual violence). Exclusion criteria are shown in the supplement. Common traumatic events that lead to attendance at the emergency department were motor vehicle accident and assaults.
The recruitment included several steps. A pre-selection screening was done each weekday morning at an out-patient clinic nearby the ED by a clinical psychologist who scanned the digital medical records of newly arrived patients in order to assess criterion A and potential exclusion criteria. Potentially eligible patients were then assessed by one of four clinical psychologists involved in the study team either in the emergency room or at bedside in the hospital ward. Already discharged patients were interviewed via telephone and, if eligible, invited to the hospital to receive the intervention in the office of the clinical psychologist. Eligible patients received both written and verbal information about the study. After signing informed consent, the psychologist conducted the baseline assessments and subsequently opened the sealed envelope containing the random assignment to either PE or active control. The intervention was delivered immediately after randomization. Participants in both groups were assessed at week 1-3 (during treatment) and after 2 and 6 months. Primary endpoint was 6 months. The participants were not reimbursed for their participation in the study.
The primary outcome was PTSD symptom severity assessed using the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) [15, 16]. The assessors (n=4) were clinical psychologists experienced in conducting structured diagnostic interviews. Each assessor had received extensive training, up to 2 ½ days, in administration and scoring of the CAPS-5. Inter-rater agreement was excellent (Inter Class Correlation between 0.91-0.98). Supervision was provided on difficult cases. Secondary outcomes were the PTSD Symptom Checklist for DSM-5 (PCL-5) , an intrusion diary [18, 19], Montgomery Åsberg Depression Rating Scale–Self rated version (MADRS-S) , the World Health Organization Disability Assessment Schedule-12 (WHODAS) , EQ-5D (Euroqol-5D)  and the Insomnia Severity Index (ISI) . Detailed information about the outcome measures are shown in the supplement.
Participants in both conditions received a three-session intervention in which the first session was provided immediately after the screening, which took place < 72 hours after the traumatic event. The therapists in the RCT were five clinical psychologists with extensive experience and training in PE. All therapists received additional training (1 day) in the adapted PE protocol used in this study and also on how to deliver the control condition treatment. Supervision was provided when needed.
Prolonged exposure (PE)
The treatment protocol from the Rothbaum et al.  study was provided to us from the study authors. The protocol was translated to Swedish by the first author, who has been trained and certified in PE by the original treatment developer (Professor Edna Foa) and who prior to the study had worked clinically with PE for 17 years. A description of the treatment protocol is provided in the supplement.
The main purpose of the control group was to provide a credible intervention that is in line with international recommendations on early interventions after trauma [13, 14]: psychoeducation about common reactions after trauma and general non-directive support aimed at promoting safety, calmness, connectedness, self-efficacy and hope. The sessions followed the same structure and were matched to the intervention in frequency and duration.
Randomisation and masking
Block randomization was conducted by an independent party (Karolinska Trial Alliance) on a 1:1 ratio. The participants were randomized after the baseline assessment using sealed envelopes. The sealed envelopes were otherwise kept safe and accessible only to persons authorized to unblind. The randomization key was kept at the clinic. Participants were blinded to the conditions in order to control for expectation confounders. Therefore, participants were simply told that they would receive one of two treatments aiming to prevent the onset of PTSD.